Miracle-dz/UniFAR-FTUs huggingface dataset:
Myogenic mechanisms in the control of systemic resistance. Introduction and historical background.

This paper surveys the early studies and ideas that led to the development of the Bayliss theory in 1902 of a pressure-dependent myogenic tone in the systemic resistance vessels; this important concept was not experimentally verified until about 50 years later. Studies of the complex interactions between this 'active' intrinsic vascular tone, 'passive' wall distensibility and tissue-produced vasodilator factors gradually led to a better understanding of local circulatory control. Precapillary smooth muscles seem to function almost like 'stretch (and/or tension? ) receptors with built-in contractility', where transmural pressure serves as a limited positive feedback and tissue vasodilator factors as a potentially powerful negative feedback. Together, these positive and negative feedback factors automatically adjust blood supply to local tissue needs and also protect the capillary exchange section from undue pressure increases thanks to the ensuing 'functional autoregulation'. Observations in these early studies also led to experimental analyses of what was later called 'structural autoregulation', as a long-term analogue to 'functional autoregulation'. 'Structural autoregulation' is the rapid morphological adaptation of the precapillary resistance vessels in hypertension whereby, by a structurally based inner radius reduction and hypertrophic wall (media) thickening, systemic resistance becomes reset upwards for functional operation at a higher pressure level. Like 'functional autoregulation', 'structural autoregulation' is essentially a local vascular response to pressure changes. Finally, myogenic activity, functional and structural autoregulation may have important cellular mechanisms in common, while 'extrinsic' influences, from nexa-connected endothelial cells and neurohormonal mechanisms for example, are likely to act as important modulators of intrinsic smooth muscle activities.
Molecular and cellular targets of anti‐IgE antibodies

Immunoglobulin E (IgE) was the last of the immunoglobulins discovered. It is present in very low amounts (nano‐ to micro‐gram per ml range) in the serum of normal healthy individuals and normal laboratory mouse strains and has a very short half‐life. This contrasts with the other immunoglobulin classes, which are present in much higher concentrations (micro‐ to milligram per ml range) and form a substantial component of serum proteins. Immunoglobulins play a role in homeostatic mechanisms and they represent the humoral arm of defence against pathogenic organisms. Since IgE antibodies play a key role in allergic disorders, a number of approaches to inhibit IgE antibody production are currently being explored. In the recent past the use of nonanaphylactic, humanized anti‐IgE antibodies became a new therapeutic strategy for allergic diseases. The therapeutic rational beyond the idea derives from the ability of the anti‐IgE antibodies to bind to the same domains on the IgE molecule that interact with the high‐affinity IgE receptor, thereby interfering with the binding of IgE to this receptor without cross‐linking the IgE on the receptor (nonanaphylactic anti‐IgE antibodies). Treatment with anti‐IgE antibodies leads primarily to a decrease in serum IgE levels. As a consequence thereof, the number of high‐affinity IgE receptors on mast cells and basophils decreases, leading to a lower excitability of the effector cells reducing the release of inflammatory mediator such as histamine, prostaglandins and leukotrienes. Experimental studies in mice indicate that injection of some monoclonal anti‐IgE antibodies also inhibited IgE production in vivo. The biological mechanism behind this reduction remains speculative. A possible explanation may be that these antibodies can also interact with membrane bound IgE on B cells, which could interfere the IgE production.
Acetylcholine suppresses the spread of excitation in the visual cortex revealed by optical recording: possible differential effect depending on the source of input

Optical recording with a voltage‐sensitive dye was performed in visual cortical slices of the rat to determine the effect of acetylcholine (ACh) on the spread of excitation. In the presence of ACh, the spread of excitation initiated by stimulation at the white matter/layer VI (WM/VI) was greatly suppressed throughout the cortex, with less suppression in the middle layers. By comparing the effect of ACh with that of 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX), the fraction of the synaptic component that was sensitive to ACh was evaluated. ACh suppressed ∼ 40–50% (maximum 55.8%, n = 11) of the initial synaptic component in the superficial and deep layers. In the middle, however, the effect was weakest and only ∼ 20–30% (minimum 20.9%, n = 11) of the initial synaptic component was suppressed. On the basis of histological analysis, the region with the weakest ACh effect extended from upper V to lower II/III. To identify the site of ACh action in terms of pre‐ versus postsynaptic localization, exogenous glutamate was applied. Because ACh did not suppress the excitation induced by glutamate, the site of the ACh action was indicated to be presynaptic. When layer II/III was stimulated instead of WM/VI, the suppression was uniform throughout the cortex. A muscarinic receptor antagonist, atropine, blocked the suppression by ACh. In conclusion, our results indicate the following two points. First, ACh strongly suppresses intracortical connectivity through presynaptic muscarinic receptors. Secondly, in contrast to the intracortical connection, some group(s) of fibres, possibly thalamocortical afferents that arise from white matter and terminate in the middle cortical layers are suppressed much less by ACh. While ACh has been reported to have confusingly diverse effects, e.g. direct depolarization and hyperpolarization as well as synaptic facilitation and suppression, its effect on the propagation of excitation is very clear; suppression on intracortical connection, leaving thalamocortical inputs rather intact. We postulate that cholinergic innervation enables the afferent input to have a relatively dominant effect in the cortex.
Lipopolysaccharide Core Glycosylation in Rhizobium leguminosarum

The lipopolysaccharide structure of the nitrogen-fixing bacterium Rhizobium leguminosarum differs from that of Escherichia coli in several ways, one of which is the sugar composition of the core. The E. coli inner core consists of 3-deoxy-D-manno-octulosonic acid (Kdo) and L-glycero-D-manno-heptose (heptose), while the inner core of R. leguminosarum contains 2-keto-3-deoxy-D-manno-octulosonic acid (Kdo), mannose, galactose, and galacturonic acid. The two Kdo residues and their linkages appear to be identical in both species. The linkages of heptose in E. coli and of mannose in R. leguminosarum to Kdo are both α1-5. We now characterize a membrane-associated glycosyl transferase in R. leguminosarum extracts that incorporates mannose into nascent lipopolysaccharide, using Kdo2-lipid IVA as the acceptor and GDP-mannose (or synthetic ADP-mannose) as the donor. The mannosyl transferase is associated with the inner membrane. The apparent Km values for GDP-mannose and Kdo2-lipid IVA are 4.3 μM and 7.1 μM, respectively, in the presence of excess co-substrate. Extracts of E. coli do not catalyze GDP-mannose-dependent glycosylation of Kdo2-lipid IVA, but they are active when ADP-mannose is substituted for GDP-mannose. Given the structural similarity of ADP-mannose to ADP-heptose, we examined the possibility that heptosyl transferase I of E. coli (the product of the rfaC gene) catalyzes mannose transfer from ADP-mannose to Kdo2-lipid IVA. Extracts of E. coli mutants defective in the rfaC gene are unable carry out ADP-mannose-dependent glycosylation of Kdo2-lipid IVA. Plasmids bearing rfaC+ not only restore the missing activity but also direct its overexpression. Our assay using ADP-mannose as a substitute for ADP-heptose (which is not readily available) should facilitate the purification and characterization of heptosyl transferase I of E. coli. The GDP-mannose-dependent enzyme of R. leguminosarum may represent a functional equivalent of E. coli RfaC.
Twenty-Five-Year Outbreak of Pseudomonas aeruginosa Infecting Individuals with Cystic Fibrosis: Identification of the Prairie Epidemic Strain

ABSTRACT Transmissible strains of Pseudomonas aeruginosa have been described for cystic fibrosis (CF) and may be associated with a worse prognosis. Using a comprehensive strain biobank spanning 3 decades, we sought to determine the prevalence and stability of chronic P. aeruginosa infection in an adult population. P. aeruginosa isolates from sputum samples collected at initial enrollment in our adult clinic and at the most recent clinic visit were examined by a combination of pulsed-field gel electrophoresis and multilocus sequence typing and compared against a collection of established transmissible and local non-CF bronchiectasis (nCFB) isolates. A total of 372 isolates from 107 patients, spanning 674 patient-years, including 66 patients with matched isolates from initial and final encounters, were screened. A novel clone with increased antibacterial resistance, termed the prairie epidemic strain (PES), was found in 29% (31/107 patients) of chronically infected patients referred from multiple prairie-based CF centers. This isolate was not found in those diagnosed with CF as adults or in a control population with nCFB. While 90% (60/66 patients) of patients had stable infection over a mean of 10.8 years, five patients experienced strain displacement of unique isolates, with PES occurring within 2 years of transitioning to adult care. PES has been present in our cohort since at least 1987, is unique to CF, generally establishes chronic infection during childhood, and has been found in patients at the time of transition of patients from multiple prairie-based CF clinics, suggesting broad endemicity. Studies are under way to evaluate the clinical implications of PES infection.
Selenium Supplementation Restores the Antioxidative Capacity and Prevents Cell Damage in Bone Marrow Stromal Cells In Vitro

Bone marrow stromal cells (BMSCs) and other cell populations derived from mesenchymal precursors are developed for cell‐based therapeutic strategies and undergo cellular stress during ex vivo procedures. Reactive oxygen species (ROS) of cellular and environmental origin are involved in redox signaling, cumulative cell damage, senescence, and tumor development. Selenium‐dependent (glutathione peroxidases [GPxs] and thioredoxin reductases [TrxRs]) and selenium‐independent (superoxide dismutases [SODs] and catalase [CAT]) enzyme systems regulate cellular ROS steady state levels. SODs process superoxide anion to hydrogen peroxide, which is subsequently neutralized by GPx and CAT; TrxR neutralizes other ROS, such as peroxinitrite. Primary BMSCs and telomerase‐immortalized human mesenchymal stem cells (hMSC‐TERT) express GPx1–3, TrxR1, TrxR2, SOD1, SOD2, and CAT. We show here that in standard cell cultures (5%–10% fetal calf serum, 5–10 nM selenite), the activity of antioxidative selenoenzymes is impaired in hMSC‐TERT and BMSCs. Under these conditions, the superoxide anion processing enzyme SOD1 is not sufficiently stimulated by an ROS load. Resulting oxidative stress favors generation of micronuclei in BMSCs. Supplementation of selenite (100 nM) restores basal GPx and TrxR activity, rescues basal and ROS‐stimulated SOD1 mRNA expression and activity, and reduces ROS accumulation in hMSC‐TERT and micronuclei generation in BMSCs. In conclusion, BMSCs in routine cell culture have low antioxi‐dative capacity and are subjected to oxidative stress, as indicated by the generation of micronuclei. Selenite supplementation of BMSC cultures appears to be an important countermeasure to restore their antioxidative capacity and to reduce cell damage in the context of tissue engineering and transplantation procedures.
Association Study between IL-1β−511 C/T Polymorphism and Obsessive-Compulsive Disorder (OCD) in Chinese Han Population

Aim: This study investigated the potential association between Obsessive-Compulsive Disorder (OCD) and a functional polymorphism of IL-1β−511 C/T in Chinese Han population. Methods: The authors genotyped the IL-1β−511 C/T of 241 OCD patients and 444 healthy control subjects and then performed a case-control association analysis. Results: No difference was found in IL-1β−511 C/T genotypic and allelic frequencies between OCD cases and controls (χ2 = 0.501, df = 2, P = 0.78 by genotype; χ2 = 0.487, df = 1, P = 0.49 by allele). Conclusion: IL-1β−511 polymorphism may not play a major role in the genetic predisposition to OCD in Chinese Han population. Given that this is an early investigation of this gene in OCD, further studies are required to draw firm conclusions.
Hyaloperonospora arabidopsidis ATR1 effector is a repeat protein with distributed recognition surfaces

The in planta association of the Hyaloperonospora arabidopsidis effector ATR1 with the cognate Arabidopsis thaliana RPP1 immune receptor activates a disease-resistance signaling pathway that inhibits pathogen growth. To define the molecular events specifying effector recognition by RPP1, we determined the crystal structure of ATR1 and assayed in planta the effects of surface polymorphisms that are critical to activating plant immunity. ATR1 adopts an elongated, all-helical, two-domain, seahorse-like structure with an overall architecture unlike any previously described fold. Structural comparisons highlight a tandemly duplicated, five-helix motif in the C-terminal domain that creates a structural framework for rapid diversification. Identification and mapping of critical recognition sites suggest that ATR1 detection by the RPP1 resistance protein is mediated by several distinct protein surfaces that allow the effectors to escape recognition through diverse surface polymorphisms. ATR1 gain-of-recognition mutants demonstrate that multiple amino acid substitutions are necessary for recognition and that surface polymorphisms exert additive effects. These results suggest that ATR1 is a modular repeat protein belonging to an ancient family of oomycete effectors that rapidly evolves to escape host detection and adopt diverse virulence functions.
Glycogen content is affected differently in acute pulmonary and extra-pulmonary lung injury

Acute respiratory distress syndrome (ARDS) is the most severe form of acute lung injury (ALI). The aim of the present study was to investigate whether paraquat-induced acute pulmonary and extra-pulmonary lung injury (ALI-P and ALI-EX, respectively), in rats, affects glycogen content in different tissues. This measurement could indicate performance limitations of tissues, a new biochemical aspect of ARDS. ALI-P and ALI-EX were induced by injection into the trachea (0.5 mg/kg) and intraperitoneally (20 mg/kg) 24 hours prior to tissue collection. The control groups (CTRL) received the same volume of saline. Glycogen content (mg/g tissue) from different tissues was measured using the anthrone reagent. Glycogen content in the heart and kidney was higher in the ALI-EX group than the CTRL-EX group. Glycogen content in the gastrocnemius muscle was lower in the ALI-EX group than the CTRL-EX group. However, there were no significant differences in glycogen content in the diaphragm in the ALI-EX and ALI-P groups or in the gastrocnemius, heart and kidney in the ALI-P group when compared to the respective controls. ALI-EX caused a greater thickening of the alveolar walls, more areas of atelectasis and a greater abundance of inflammatory cells in comparison to ALI-P. These results demonstrate that glycogen content in ALI, induced by an herbicide that is highly toxic to humans and animals, is altered in different tissues depending on the location of the injury.
Local government spending: where is the axe falling?

• Local government spending varies significantly across England. Excluding education, local government expenditure per person in London in 2009−10 (£1,868) was much higher than that in the rest of the country, and almost double that in the South East of England (£976), the region with the lowest spending. Higher spending on transport and police in London explains a large part of this difference. More generally, spending is higher in poorer, more urban districts and lower in more affluent, rural and suburban districts.
Defining the radiation chemistry during liquid cell electron microscopy to enable visualization of nanomaterial growth and degradation dynamics

We present a critical review of methods for defining the chemical environment during liquid cell electron microscopy investigation of electron beam induced nanomaterial growth and degradation. We draw from the radiation chemistry and liquid cell electron microscopy literature to present solution chemistry and electron beam–based methods for selecting the radiolysis products formed and their relative amount during electron irradiation of liquid media in a transmission electron microscope. We outline various methods for establishing net oxidizing or net reducing reaction environments and propose solvents with minimal overall production of radicals under the electron beam. Exemplary liquid cell electron microscopy experiments in the fields of nanoparticle nucleation, growth, and degradation along with recommendations for best practices and experimental parameters are reported. We expect this review will provide researchers with a useful toolkit for designing general chemistry and materials science liquid cell electron microscopy experiments by ‘directing’ the effect of the electron beam to understand fundamental mechanisms of dynamic nanoscale processes as well as minimizing radiation damage to samples.
Significance of absorption, oxidation, and binding to toxicity of four ecdysone agonists in multi-resistant cotton leafworm.

Treatment of last-instar larvae of multi-resistant cotton leafworm Spodoptera littoralis with four dibenzoylhydrazines, methoxyfenozide (RH-2485), tebufenozide (RH-5992), halofenozide (RH-0345), and RH-5849, resulted in premature molting leading to death. Methoxyfenozide was the most toxic followed by tebufenozide, halofenozide, and RH-5849. To explain differences in toxicity, especially between multi-resistant and laboratory strains, absorption in the body tissues and oxidative metabolism were tested with 14C-labeled ecdysone agonist and a Lineweaver-Burk assay, respectively. Then to address different compound potencies in multi-resistant strains, the potency of the four ecdysone agonists was measured based on their ability to mimic the natural insect molting hormone, 20-hydroxyecdysone (20E) by inducing evagination in isolated imaginal wing discs. Using monoclonal antibody 9B9, the presence of ecdysteroid receptors in imaginal discs in vitro was confirmed. In parallel, Scatchard plot analysis with whole imaginal wing discs cultured with different concentrations of 3H-labeled ponasterone A indicated no significant difference in affinity and in number of target sites for binding between multi-resistant and susceptible laboratory strains. The four compounds tested caused the effect as agonists of 20E in vitro, and typically the order of their toxicities (LC50s) corresponded with that for evagination-induction with whole imaginal discs.
Bacterial Artificial Chromosome-Based Experimental Strategies in the Field of Developmental Neuroscience

Bacterial artificial chromosomes (BACs) constitute minimal components of various whole genome-sequencing projects, including our own. The recent innovation of efficient recombinogenic bacterial strains allows systematic BAC modifications (i.e. recombineering; Reviewed in Copeland et al., 2001), setting BACs as an ideal experimental basis for functional genomics with their broad coverage of transcriptional regulatory elements. For instance, in the field of neuroscience, the GENSAT project extensively modified mouse BAC clones, covering gene transcriptional units preferentially expressed in the nervous system, and generated hundreds of BAC transgenic (Tg) mouse lines from those modified BACs (Gong et al., 2003). These BAC-Tg lines successfully recapitulated complex gene expression profiles in the nervous system (Gong et al., 2003), providing a rigid analytical platform so as to be able to answer the fundamental question of how tens of millions of neurons and thousands of cell-types can become elaborate interconnected circuitries in the brain by using only twenty-thousand sets of gene transcriptional activities.
Entrepreneurial Processes of Business Cluster Formation and Growth by ‘Habitual’ Entrepreneurs

Previous studies on habitual entrepreneurs have not researched in any depth the processes and strategies associated with the growth of business clusters by habitual entrepreneurs. To gain insights into these issues, case studies were conducted with habitual entrepreneurs who owned high-growth businesses in Scotland. The research involved the analysis of life histories and business genealogies. A diversity was found in the backgrounds of the entrepreneurs studied, in the types of ventures founded, and in strategies adopted to build up their cluster of companies. Entrepreneurial motives, strategies, and practices by habitual entrepreneurs in building their business ownership clusters not only can differ markedly from one entrepreneur or type of entrepreneur to another, but also by individual entrepreneurs over time. Despite this diversity, little evidence emerged that the growth of business ownership clusters was motivated by orthodox corporate management principles, though corporate management practices were employed in some cases to subsequently assimilate the new venture into a cluster. On balance, entrepreneurial opportunism was more prevalent than planned “survivalist” diversification. Further, the concept of “entrepreneurial” performance is introduced to distinguish performance through creating a cluster of ventures rather than through growing a single one.
Performance analysis of adaptive wavelet denosing by speech discrimination and thresholding

The performance of automatic speech recognition can be elevated either at the front end by pattern recognition, speech enhancement or by a powerful classifier at the backend. A adaptive time space strategy is applied to Bayes threshold and Universal threshold denoising techniques, to enhance the signal to noise ratio of noisy speech and principle of speech discrimination from silence is employed before speech enhancement, to prevent the over thresholding of speech coefficients for maintaining the intelligibility of speech. The experimental results reveal that performance of time space adaptive Bayes shrink denoising principle outperforms the later in enhancing signal to noise ratio of noisy speech while retaining the speech intelligibility.
Adaptive Background Updating Algorithm in Complex Scene

A common method for real-time video detection in image sequences involves “background subtraction”. The numerous approaches to this problem differ in the type of background model. This paper discus a new background updating method based on classification. A growth template that can detect the target and Interference, like noise, has put forward. This template can choose the growth direction automatically according to the characteristic around the pixel, the template can eliminate the errors that accumulated by the noise; implement background updating when many targets appeared. Experiment is presented for comparison between the proposed method and the conventional way, and the results show that the proposed method will stabilize within a very short time when quick changes in the scene. This system is flexible enough to handle variations in moving objects and other arbitrary changes to the observed scene.