Miracle-dz/UniFAR-FTUs huggingface dataset:
NOX4 NADPH Oxidase-Dependent Mitochondrial Oxidative Stress in Aging-Associated Cardiovascular Disease.

AIMS Increased oxidative stress and vascular inflammation are implicated in increased cardiovascular disease (CVD) incidence with age. We and others demonstrated that NOX1/2 NADPH oxidase inhibition, by genetic deletion of p47phox, in Apoe(-/-) mice decreases vascular reactive oxygen species (ROS) generation and atherosclerosis in young age. The present study examined whether NOX1/2 NADPH oxidases are also pivotal to aging-associated CVD. RESULTS Both aged (16 months) Apoe(-/-) and Apoe(-/-)/p47phox(-/-) mice had increased atherosclerotic lesion area, aortic stiffness, and systolic dysfunction compared with young (4 months) cohorts. Cellular and mitochondrial ROS (mtROS) levels were significantly higher in aortic wall and vascular smooth muscle cells (VSMCs) from aged wild-type and p47phox(-/-) mice. VSMCs from aged mice had increased mitochondrial protein oxidation and dysfunction and increased vascular cell adhesion molecule 1 expression, which was abrogated with (2-(2,2,6,6-Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl)triphenylphosphonium chloride (MitoTEMPO) treatment. NOX4 expression was increased in the vasculature and mitochondria of aged mice and its suppression with shRNA in VSMCs from aged mice decreased mtROS levels and improved function. Increased mtROS levels were associated with enhanced mitochondrial NOX4 expression in aortic VSMCs from aged subjects, and NOX4 expression levels in arterial wall correlated with age and atherosclerotic severity. Aged Apoe(-/-) mice treated with MitoTEMPO and 2-(2-chlorophenyl)-4-methyl-5-(pyridin-2-ylmethyl)-1H-pyrazolo[4,3-c]pyridine-3,6(2H,5H)-dione had decreased vascular ROS levels and atherosclerosis and preserved vascular and cardiac function. INNOVATION AND CONCLUSION These data suggest that NOX4, but not NOX1/2, and mitochondrial oxidative stress are mediators of CVD in aging under hyperlipidemic conditions. Regulating NOX4 activity/expression and using mitochondrial antioxidants are potential approaches to reducing aging-associated CVD.
The Impact of Leverage Variances on Growth: A Longitudinal Study of Pakistanâ€™s Corporate Sector

This study is an empirical investigation into the impact of leverage deviations from the target on growth of companies listed on the Karachi Stock Exchange (KSE). It is posited that leverage variance impedes the growth of firms. The role of leverage deviations from the target on firmsâ€™ growth is analyzed by applying dynamic panel methodology of firmsâ€™ level annual accounting data. The results indicate that size of the firm, profitability, collateral values of assets, non-debt tax shield, firm-specific interest rate and spontaneous finance are significant determinants of the target leverage. It is found that firms, seldom have actual leverage equal to the target leverage, and more often the actual leverage deviate from the target level. This deviation, adversely affects the growth of firms. The empirical results indicate that upward deviation and downward deviation affect the companyâ€™s growth, differently. It is concluded that over-levered firmsâ€™ growth is more sensitive to leverage variance as compared to the under-levered firms.
A new KCNQ1 mutation at the S5 segment that impairs its association with KCNE1 is responsible for short QT syndrome.

AIMS KCNQ1 and KCNE1 encode Kv7.1 and KCNE1, respectively, the pore-forming and the accessory subunits of the slow delayed rectifier potassium current, IKs. KCNQ1 mutations are associated with long and short QT syndrome. The aim of this study was to characterize the biophysical and cellular phenotype of a KCNQ1 missense mutation, F279I, found in a 23-year-old man with a corrected QT interval (QTc) of 356 ms and a family history of sudden cardiac death. METHODS AND RESULTS Experiments were performed using perforated patch-clamp, western blot, co-immunoprecipitation, biotinylation, and immunocytochemistry techniques in HEK293, COS7 cells and in cardiomyocytes transfected with WT Kv7.1/KCNE1 or F279I Kv7.1/KCNE1 channels. In the absence of KCNE1, F279I Kv7.1 current exhibited a lesser degree of inactivation than WT Kv7.1. Also, functional analysis of F279I Kv7.1 in the presence of KCNE1 revealed a negative shift in the activation curve and an acceleration of the activation kinetics leading to a gain of function in IKs. The co-assembly between F279I Kv7.1 channels and KCNE1 was markedly decreased compared with WT Kv7.1 channels, as revealed by co-immunoprecipitation and Föster Resonance Energy Transfer experiments. All these effects contribute to the increase of IKs when channels incorporate F279I Kv7.1 subunits, as shown by a computer model simulation of these data that predicts a shortening of the action potential (AP) consistent with the patient phenotype. CONCLUSION The F279I mutation induces a gain of function of IKs due to an impaired gating modulation of Kv7.1 induced by KCNE1, leading to a shortening of the cardiac AP.
The State of ICT in South Africa

=2663055 or http://dx.doi. org/10.2139/ssrn.2663055 ). 56. MyBroadband (2014). “They’re after our billions! USAASA”. Available at: https://mybroadband.co.za/news/government/99798-theyre-after-our-billions-usaasa.html 57. ITWeb (2018). “Set-top box manufacturing war looms”. Available at: https://www.itweb. co.za/content/O2rQGqAp8NWMd1ea TechCentral (2018). “USAASA CEO suspended after breakdown with board”. Available at: https://techcentral.co.za/ usaasa-ceo-suspended-after-breakdown-with-board/81030/ 58. TechCentral (2017). “Set-top box dispute goes to arbitration”. Available at: https://techcentral.co.za/ set-top-box-dispute-goes-to-arbitration/71587/
RESPONSE OF MYZUS PERSICAE ( SULZER ) TO IMIDACLOPRID AND THIAMETHOXAM ON SUSCEPTIBLE AND RESISTANT POTATO VARIETIES

Among insect pests the Green peach aphid Myzus persicae (Sulzer) is one of the most damaging virulent insect to potato crop. Research experiment was conducted at Research Farm of Khyber Pakhtunkhwa Agricultural University Peshawar, Pakistan during spring 2008 to test two insecticides against Myzus persicae on two potato varieties viz Kuroda and Desiree. The results revealed that both the insecticides Provado 1.6F (imidacloprid) and Actara 25WG (thiamethoxam) significantly suppressed the Myzus persicae population by 74.92 and 67.79%, respectively. Considering the population difference as a parameter, Provado reduced dose was less toxic to Myzus persicae than its labeled dose (4.7%) but it was significantly more toxic than the labeled and reduced doses of Actara by 2.03 and 7.49%, respectively. The population of Myzus persicae on Kuroda control plants was lesser than Desiree by 45.8%. Excluding this difference; the foliar insecticides reduced Myzus persicae on Kuroda more than Desiree by 0.5%. The difference between labeled and reduced doses of foliar insecticides, to reduce Myzus persicae population, on Kuroda was 5.7% and on Desiree it was 4.8%. Comparison of Kuroda and Desiree showed that Kuroda treated with reduced doses of insecticides, except Kuroda treated with labeled doses, had smaller population of Myzus persicae than the Desiree treated with both the doses of insecticides. Significantly highest tuber yield was obtained from plants treated with Provado reduced and labeled doses (both not significantly different). On average, Kuroda yielded significantly higher than Desiree.
Knowledge Transfer in Audit Firms*

We utilize the setting of the rapid audit market consolidation in China over the past twenty years to study knowledge transfer in audit firms. We employ a difference-in-difference approach and examine whether industry-specific knowledge transfer occurs after a merger of two audit firms with different levels of expertise in a particular industry. For clients in an industry audited by both merging audit firms, those audited by the less competent audit firm in that industry belong to the treatment group, while all other clients belong to the control group. Consistent with the existence of knowledge transfer, we find an economically significant improvement in audit quality (as reflected in a reduction in misstatements and an increase in modified audit opinions) for the treatment group relative to the control group in the same merged audit firm.
Comparison of Western immunoblots and gene detection assays for identification of potentially enterotoxigenic isolates of Clostridium perfringens

Clostridium perfringens enterotoxin (CPE) is an important sporulation-associated virulence factor in several illnesses of humans and domestic animals, including C. perfringens type A food poisoning. Therefore, the ability to determine the enterotoxigenicity of food or fecal C. perfringens isolates with simple, rapid assays should be helpful for epidemiologic investigations. In this study, Western immunoblotting (to detect CPE production in vitro) was compared with PCR assays and digoxigenin-labeled probe assays (to detect all or part of the cpe gene) as a method for determining the enterotoxigenicity of C. perfringens isolates. The cpe detection assays yielded reliable results with DNA purified from vegetative C. perfringens cultures, while Western immunoblots required in vitro sporulation of C. perfringens isolates to detect CPE production. Several cpe-positive C. perfringens isolates from diarrheic animals did not sporulate in vitro under commonly used sporulation-inducing conditions and consequently tested CPE negative. This result indicates that cpe gene detection and serologic CPE assays do not necessarily yield similar conclusions about the enterotoxigenicity of a C. perfringens isolate. Until further studies resolve whether these cpe-positive isolates which do not sporulate in vitro can or cannot sporulate and produce CPE in vivo, it may be preferable to use cpe detection assays for evaluating C. perfringens isolate enterotoxigenicity and thereby avoid potential false-negative conclusions which may occur with serologic assays.
High pressure X-ray studies at NSLS

The National Synchrotron Light Source offers the COMPRES community a considerable opportunity for x-ray studies using the superconducting wiggler at X17. This beamline has a steep history of high pressure innovations including diamond anvil studies and large volume studies. The superconducting wiggler continues to provide an x-ray source that is competitive with third generation sources for x-ray diffraction studies. In addition, the current plans to build the next x-ray synchrotron at Brookhaven (NSLSII) provides a significant future at the NSLS that requires the presence of COMPRES research to assure access to the NSLSII. With this vision of the NSLS, we held a workshop on February 25 – 26 to assess the community needs and hopes for the next five years. Forty five attendees discussed the strengths and weaknesses, the science goals and technical limitations. We enumerated the needs for support staff and the needs for new equipment to enable initiatives. We set priorities and estimated budgets. Here we present the results of the workshop and provide a budget plan for the next five years. We include a list of participants and the agenda for the workshop as appendices Here we address some of the conclusions of the workshop followed by the detailed proposal for the next five years.
A control algorithm for compensation of customer-generated harmonics and reactive power

This paper presents a new control algorithm for a shunt active power filter to compensate harmonics and reactive power required by nonlinear loads. If the utility voltage is distorted, active power filter (APF) allows similar level of distortion in the compensated source current. Therefore, the resultant source currents have the same waveform as that of the supply voltage, thereby attributing the responsibility of utility and customer at the point of common coupling (PCC). Due to similar shape of the source voltage and currents, reactive power is compensated completely. The proposed scheme provides an additional feature of compensation of either only harmonics, or both harmonics and reactive power simultaneously, based on the desired capacity of the APF. Various simulation results are presented with ideal and distorted mains voltage and compared with other algorithms. Proposed algorithm is implemented as a prototype to verify the simulation results.
Inhibition of biomaterial‐induced complement activation attenuates the inflammatory host response to implantation

Although complement is a known contributor to biomaterial‐induced complications, pathological implications and therapeutic options remain to be explored. Here we investigated the involvement of complement in the inflammatory response to polypropylene meshes commonly used for hernia repair. In vitro assays revealed deposition of complement activation fragments on the mesh after incubation in plasma. Moreover, significant mesh‐induced complement and granulocyte activation was observed in plasma and leukocyte preparations, respectively. Pretreatment of plasma with the complement inhibitor compstatin reduced opsonization >2‐fold, and compstatin and a C5a receptor antagonist (C5aRa) impaired granulocyte activation by 50 and 67%, respectively. We established a clinically relevant mouse model of implantation and could confirm deposition of C3 activation fragments on mesh implants in vivo using immunofluorescence. In meshes extracted after subcutaneous or peritoneal implantation, the amount of immune cell infiltrate in mice deficient in key complement components (C3, C5aR), or treated with C5aRa, was approximately half of that observed in wild‐type littermates or mice treated with inactive C5aRa, respectively. Our data suggest that implantation of a widely used surgical mesh triggers the formation of an inflammatory cell microenvironment at the implant site through complement activation, and indicates a path for the therapeutic modulation of implant‐related complications. —Kourtzelis, I. , Rafail, S. , DeAngelis, R. A. , Foukas, P. G. , Ricklin, D. , Lambris, J. D. Inhibition of biomaterial‐induced complement activation attenuates the inflammatory host response to implantation. FASEB J. 27, 2768‐2776 (2013). www.fasebj. org
Mutational Status in Pediatric Thyroid Cancer

Data from the National Cancer Institute Surveillance, Epidemiology, and End Results registry demonstrate a rising incidence of thyroid cancer in patients under the age of 20 [1–3]. Children with thyroid cancer tend to present with more advanced disease than their adult counterparts [4–6]. At presentation, the incidence of lymph node involvement in children (40–90%) is roughly double that of adults (20–30%). Distant metastases are present in 20–30% of children at diagnosis, compared to 2% in adults [7]. However, overall survival in the pediatric population remains excellent with 30-year overall survival rates of 90–99% [7]. Most pediatric patients are treated with surgery followed by radioactive Iodine [7–9]. Due to the more advanced stage at presentation in children, extensive and repeated treatment is often required [7,8,10]. Thyroid cancer in children is in many ways a distinct disease from thyroid cancer in adults. Currently, there is no clear explanation for the dissimilarities in clinicopathologic outcomes of thyroid cancer in pediatric and adult populations. Histologically, papillary thyroid cancer (PTC) is the most prevalent type of thyroid malignancy in both children and adults [11]. Mutations in the BRAF gene are common in patients with PTC. Themajority of these mutations involve a transversion from T to A at nucleotide 1799, leading to a valine to glutamic acid change in codon 600. This results in the BRAF mutation (termed BRAF mutation hereafter). In adult patients, this mutation occurs in around 50% of patients, although reports vary from 29–83% in the literature [12–14]. Previous reports specific to pediatric patients have shown a lower prevalence of this point mutation in childhood thyroid carcinoma, although the numbers of patients tested were limited [7,15–17]. It has been suggested that differences in the biomolecular profiles of thyroid carcinoma, such as presence or absence of the BRAF mutation, might account for some of the differences between childhood and adult thyroid cancers [11,15–18]. This retrospective analysis of pediatric papillary thyroid carcinoma (PTC) aimed to determine the prevalence of the BRAF mutation and review the clinicopathologic outcomes of pediatric patients treated at our institution. Specifically, age, gender, race, tumor characteristics, and BRAF mutational status were analyzed for possible correlations with outcome.
Influence of Outer Surface Protein A Antibody onBorrelia burgdorferi within Feeding Ticks

ABSTRACT Borrelia burgdorferi, the spirochetal agent of Lyme disease, is transmitted by Ixodes ticks. When an infected nymphal tick feeds on a host, the bacteria increase in number within the tick, after which they invade the tick’s salivary glands and infect the host. Antibodies directed against outer surface protein A (OspA) of B. burgdorferi kill spirochetes within feeding ticks and block transmission to the host. In the studies presented here, passive antibody transfer experiments were carried out to determine the OspA antibody titer required to block transmission to the rodent host. OspA antibody levels were determined by using a competitive enzyme-linked immunosorbent assay that measured antibody binding to a protective epitope defined by monoclonal antibody C3.78. The C3.78 OspA antibody titer (>213 μg/ml) required to eradicate spirochetes from feeding ticks was considerably higher than the titer (>6 μg/ml) required to block transmission to the host. Although spirochetes were not eradicated from ticks at lower antibody levels, the antibodies reduced the number of spirochetes within the feeding ticks and interfered with the ability of spirochetes to induceospC and invade the salivary glands of the vector. OspA antibodies may directly interfere with the ability of B. burgdorferi to invade the salivary glands of the vector; alternately, OspA antibodies may lower the density of spirochetes within feeding ticks below a critical threshold required for initiating events linked to transmission.
Individualized Knowledge Graph: A Viable Informatics Path to Precision Medicine

We present here a vision of individualized Knowledge Graphs (iKGs) in cardiovascular medicine: a modern informatics platform of exchange and inquiry that comprehensively integrates biological knowledge with medical histories and health outcomes of individual patients. We envision that this could transform how clinicians and scientists together discover, communicate, and apply new knowledge . What if physicians had their own personal artificial intelligence assistant—similar to Tony Stark’s J.A. R.V. I.S. —to help prescribe individualized strategies for patient care? In our era of digital biomedicine, this symbiotic human–machine interaction has for the first time become a feasible reality. We have at our fingertips the depth, dimension, and scale of information to piece together a holistic picture of disease and the human condition; however, the human capacity to analyze and extract knowledge is limited, and collaborations with computers could drastically enhance the power and speed at which an integrated view of disease is synthesized.1 Beginning in 2017, 1 million Americans will participate in the Precision Medicine Initiative All of Us Research Program. Moreover, the National Institutes of Health Precision Medicine Initiative Cohort Program2–4 calls for a knowledge network that uses biomedical informatics to bridge basic biological knowledge on molecular disease drivers with higher-level phenotypic abstractions representing a patient’s clinical manifestation. This network could link evidence across methods used to characterize a disease process, hone disease classification, sharpen treatment regimens, and tailor preventative strategies for specific individuals. Both current and emerging informatics developments have shaped everyday clinical practice, including but not limited to echocardiographic pattern recognition,5 Framingham Risk Score,6 and random survival forests for predicting survival in systolic heart failure.7 In our view, these studies have begun to explore the promise of modern biomedical informatics. In the last decade, integrated omics science has provided unmatched power for unbiased characterization of …
A Least-Squares Strain Estimator for Elastography

A least-squares strain estimator (LSQSE) for elastography is proposed. It is shown that with such an estimator, the signal-to-noise ratio in an elastogram (SNRe ) is significantly improved. This improvement is illustrated theoretically using a modified strain filter and experimentally using a homogeneous gel phantom. It is demonstrated that the LSQSE results in an increase of the elastographic sensitivity (smallest strain that could be detected), thereby increasing the strain dynamic range. Using simulated data, it is shown that a tradeoff exists between the improvement in SNRe and the reduction of strain contrast and spatial resolution.
What Makes a Good Data Model? Evaluating Quality of Entity Relationship Models

This paper develops a framework for evaluating the quality of data models and choosing between alternative representations of requirements. For any particular set of user requirements there are many possible models, each of which has drastically different implications for database and systems design. In the absence of formally defined and agreed criteria, the choice of an appropriate representation is usually made in an ad hoc way, based on personal opinion. The evaluation framework proposed consists of four major constructs: qualities (desirable properties of a data model), metrics (ways of measuring each quality), weightings (relative importance of each quality) and strategies (ways of improving data models). Using this framework, any two data models may be compared in an objective and comprehensive manner. The evaluation framework also builds commitment to the model by involving all stakeholders in the process: end users, management, the data administrator and application developers.
Molecular modifiers of T cell antigen receptor triggering threshold: the mechanism of CD28 costimulatory receptor

CD28 was thought to represent a prototypic membrane receptor responsible for delivering the classically defined ‘second signal’ needed to avoid T cell paralysis when recognizing antigen presented by appropriate antigen presenting cells (APCs). Almost two decades after its molecular identification, the mechanism by which this ‘second receptor’ facilitates clonal expansion and differentiation upon antigen encounter is still not fully elucidated. There may be at least two reasons for this partially gray picture: the use of nonphysiological experimental conditions to study it and the fact that the action of CD28 may be partly masked by the presence of additional T cell surface receptors that also provide some costimulatory signals, although not equivalent to the one delivered through CD28. Thus, instead of aging, the study of CD28 is still a topical subject. What is appearing through work of recent years is that far from being purely qualitative, the CD28 signal provides a key quantitative contribution to potently boost the T cell antigen receptor (TCR) signal. In other words, CD28 is in part a signaling ‘sosia’ of the TCR. Also, it is clear now that CD28 operates via multiple molecular effects. Still, what we do not understand is the ‘qualitative’ part of this signal, perhaps due to lack of identification of unique signaling components and/or pathways activated by CD28 only. Here we review a series of recent findings pointing towards novel avenues to better understand the molecular basis of CD28 function.