Miracle-dz/UniFAR-FTUs huggingface dataset:
Mannheimia haemolytica Leukotoxin Activates a Nonreceptor Tyrosine Kinase Signaling Cascade in Bovine Leukocytes, Which Induces Biological Effects

ABSTRACT The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces biological effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any effects. These findings suggest that the specificity of LktA effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to biological effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for biological effects. We used a biologically inactive mutant leukotoxin (ΔLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The ΔLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3′-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced biological effects.
Valosin‐containing protein/p97 interacts with sperm‐activating and sperm‐attracting factor (SAAF) in the ascidian egg and modulates sperm‐attracting activity

Sperm chemotaxis toward an egg is observed in many animals, and the control of sperm‐attracting activity is thought to play an important role in ensuring fertilization. However, the mechanism underlying the release of a sperm attractant from an egg is still obscure. In this study, we examined the systems involved in the release of sperm‐activating and sperm‐attracting factor (SAAF), which is the sperm attractant of the ascidian Ciona intestinalis. Here, we show that the egg acquires sperm‐attracting activity after germinal vesicle breakdown. Further, since the cytoplasmic extracts of immature oocytes exhibit no sperm‐attracting activity, the SAAF in oocytes may be activated after germinal vesicle breakdown. We found 13 SAAF‐binding proteins in an egg plasma membrane extract and identified five proteins by proteomic analysis: valosin‐containing protein (VCP)/p97, proteasome alpha 2 subunit, MGC97756 protein, proteasome subunit Y, and beta‐tubulin. In particular, the interaction between VCP/p97 and SAAF was confirmed by a pull‐down assay. VCP/p97 is initially localized in the germinal vesicle, and during oocyte maturation, it shifts to the endoplasmic reticulum in the cortical regions. Thus, VCP/p97 is a potential modulator of SAAF release from the egg.
Survival of the fastest: On the origin of premature ejaculation

Abstract The common problem of premature ejaculation is explained in terms of evolutionary adaptation. Based on findings from primate behaviors, I hypothesize that those protohominids who were rapid ejaculators (perhaps with a highly sensitive glans) were less likely to be repelled by the females and/or attacked by other sexually aroused males. As a result, they had more opportunities to copulate and to impregnate. Thus, the likelihood that speedy ejaculation would be represented in the succeeding generations was progressively increased. Hence, male Homo sapiens today are over‐represented with individuals possessing this once superior trait. I further argue that premature ejaculation has become dysfunctional only in recent times as a consequence of the lag between biological and social changes.
Central obesity and the Mediterranean diet: A systematic review of intervention trials

ABSTRACT Central obesity is associated with chronic low-grade inflammation, and is a risk factor for cardiometabolic syndrome. The Mediterranean diet pattern has a convincing evidence-base for improving cardiometabolic health. This review investigated the impact of Mediterranean diet interventions on central obesity, specifically. A systematic literature search was conducted in the MEDLINE, CINAHL, EMBASE and Cochrane library databases. Search terms included: ‘Mediterranean Diet’, ‘Mediterranean dietary pattern’, ‘central obesity’ and ‘visceral fat’. The search was limited to English language and humans ≥18 years. Eighteen articles met the eligibility criteria and reported at least one outcome measure of central obesity with Mediterranean diet intervention. Central obesity measures included waist circumference (16 studies), waist-hip ratio (5 studies) and visceral fat (2 studies). Thirteen (72%) of the studies, totaling 7186 subjects (5168 subjects assigned to a Mediterranean Diet), reported a significant reduction in central obesity with a Mediterranean-type diet. However, seven out of these 13 interventions employed energy restriction, and only three showed a statistically significant favorable effect of the Mediterranean diet relative to a control group. This systematic review highlights the potential for a Mediterranean diet intervention to reduce central obesity and in turn reduce obesity-related chronic disease risk and associated public health burden.
Engineering and Economic Applications of Complementarity Problems

This paper gives an extensive documentation of applications of finite-dimensional nonlinear complementarity problems in engineering and equilibrium modeling. For most applications, we describe the problem briefly, state the defining equations of the model, and give functional expressions for the complementarity formulations. The goal of this documentation is threefold: (i) to summarize the essential applications of the nonlinear complementarity problem known to date, (ii) to provide a basis for the continued research on the nonlinear complementarity problem, and (iii) to supply a broad collection of realistic complementarity problems for use in algorithmic experimentation and other studies.
Transcriptional regulation of miR-196b by ETS2 in gastric cancer cells

E26 transformation-specific sequence (ETS)-2 is a transcriptional modulator located on chromosome 21, alterations in its expression have been implicated with a reduced incidence of solid tumors in Down syndrome patients. MicroRNAs (miRNAs) are thought to participate in diverse biological functions; however, the regulation of miRNAs is not well characterized. Recently, we reported that miR-196b is highly expressed in gastric cancers. Herein, we demonstrate that miR-196b expression was significantly repressed by ETS2 during gastric cancer oncogenesis. We demonstrate that knockdown of endogenous ETS2 expression increases miR-196b expression. A genomic region between −751 and −824 bp upstream of the miR-196b transcriptional start site was found to be critical for the repression activity. This putative regulatory promoter region contains three potential ETS2-binding motifs. Mutations within the ETS2 binding sites blocked the repression activity of ETS2. Furthermore, knockdown of ETS2 or overexpression of miR-196b significantly induced migration and invasion in gastric cancer cells. In addition, alterations in ETS2 and miR-196b expression in gastric cancer cell lines affected the expression of epithelial–mesenchymal transition-related genes. The levels of vimentin, matrix metalloproteinase (MMP)-2 and MMP9 were drastically induced, but levels of E-cadherin were decreased in shETS2- or miR-196b-transfected cells. Our data indicate that ETS2 plays a key role in controlling the expression of miR-196b, and miR-196b may mediate the tumor suppressor effects of ETS2. We demonstrated that miR-196b was transcriptionally regulated by ETS2 and there was an inverse expression profile between miR-196b and ETS2 in clinical samples. This finding could be beneficial for the development of effective cancer diagnostic and alternative therapeutic strategies.
Simulation of Fuzzy PI Controller for ABS based on Electromechanical brake system

A PI controller for anti-lock braking system, whose parameters can be adjusted automatically, was designed with fuzzy algorithm. At the same time, a controller of servo motor which adopted force control architecture with cascaded force, speed and current control loops, was designed. Simplified models such as motor, vehicle and tire model were erected. Computer simulation on various typical conditions show that wheel slip in braking wheel can be restricted in optimum value by controlling clamping force, motor velocity and motor current synthetically.
Impact of synchronization on receiver performance in wideband CDMA networks

Synchronization may severely impact the capacity or spectrum efficiency of wideband CDMA networks. Evaluations of the uplink capacity for improved STAR and the 2D-RAKE with both perfect and active synchronization indicate that synchronization with the early-late gate component of a RAKE-type receiver may constitute a bottleneck for any performance improvement. Enhancement of synchronization remains a key issue. Results also suggest that STAR offers a promising alternative to the 2D-RAKE with early-late gate, offering on average an increase in spectrum efficiency of more than 100% in the presence of synchronization errors at both data rates of 9.6 and 144 kbps.
Personas is applicable: a study on the use of personas in Denmark

The persona method is gaining widespread use and support. Many researchers have reported from single cases and novel domains how they have used the method. Few have conducted literature studies in order to identify and discuss the different understandings of the method. Fewer still have reported on ethnographic studies of practice. This paper falls within the last category, reporting on a study on how practitioners in Denmark use the method, and their perceptions of benefits and challenges when using the method. Finally, different casts of personas obtained from the involved companies are analyzed. The findings are compared to reported studies of practice. Contrary to the existing findings the study reports that the method is well integrated into existing practices.
Efficacy of Abelcet and caspofungin, alone or in combination, against CNS aspergillosis in a murine model.

OBJECTIVES Currently, few options exist to treat central nervous system (CNS) aspergillosis, which is usually fatal. We tested the efficacy of Abelcet and caspofungin, alone and in combination for treatment of this disease. METHODS Male CD-1 mice were immunosuppressed with 200 mg/kg cyclophosphamide 2 days prior to infection and every 5 days thereafter. In the first study, mice were infected intracerebrally with 2.1 x 10(6) conidia/mouse of Aspergillus fumigatus; 10 days of once daily therapy began one day later. Groups of 10 received 0.8, 4, or 8 mg/kg of Abelcet, intravenously (iv), or caspofungin, intraperitoneally, 0.8 mg/kg of conventional amphotericin B (AmB) iv, or no treatment. In a second study, mice were challenged with 6.4 x 10(6) conidia and given no treatment, 8 mg/kg of Abelcet or caspofungin, alone or in combination. On day 14, cfu were determined in survivors by plating of organ homogenates. RESULTS In the first study, mice given any regimen of Abelcet or caspofungin had a survival rate > or =80% whereas untreated had 90% mortality. All drug regimens prolonged survival (P < or = 0.0008) and reduced cfu (P < or = 0.0001-0.003) recovered from the brains and kidneys compared with untreated. Abelcet showed an apparent dose-related reduction of cfu in the brains. Abelcet at 4 or 8 mg/kg were equivalent to AmB in reducing cfu from both organs (P > 0.05); AmB was superior to 0.8 mg/kg of Abelcet in the brain only (P < 0.02). Abelcet at 8 mg/kg or AmB at 0.8 mg/kg were superior to all regimens of caspofungin in reducing cfu (P < or = 0.05-0.001). In the second study, Abelcet alone significantly prolonged survival and reduced cfu in the organs versus the controls. Caspofungin did not significantly prolong survival or reduce cfu in comparison with the controls. In combination, Abelcet and caspofungin were equivalent to Abelcet alone. CONCLUSIONS Abelcet proved to be efficacious, but not curative, in the treatment of CNS aspergillosis and was equivalent overall to conventional AmB. Caspofungin was not as effective against the larger inoculum, but did not enhance or interfere with the efficacy of Abelcet. Since Abelcet displayed dose-responsive efficacy, it is possible higher doses could produce superior results, yet not show toxicity.
An overview of ethnicity and assessment of family history in primary care settings

Purpose: To discuss the importance of and the nurse practitioner’s (NP’s) role in the assessment of ethnicity/family of origin in conducting a multigenerational family history in primary care settings. Data sources: A review of the literature on past research results addressing racial and ethnic disparities and current articles from scientific journals exploring the relationship between race and genetics. Web sites were from the National Institutes of Health, the Human Genome Research Institute, the National Cancer Institute, and the Health and Human Services Minority Health and Disparities report. Conclusions: The family history has received renewed interest due to the sequencing of the human genome. A multigenerational family history is an important first step in screening for a multitude of disorders impacted by genetic susceptibility, shared environments, and common behaviors. Assessment of the patient’s ethnicity/family of origin is an integral part of the multigenerational family history, particularly in the diagnosis of chronic diseases and the assessment of risks for genetic disorders. The multigenerational family history is important in diagnosis, predictive genetic testing, disease prevention, and health promotion. Challenges facing NPs and the utilization of a multigenerational family history in the current U.S. health system include (a) training clinicians on the correct assessment and utilization of a multigenerational family history, (b) assessment of the subtleties of ethnicity and identifying multiple ethnic groups within a family, (c) collection of the family history in a manner that is sensitive to the cultural beliefs of individuals, and (d) avoidance of stereotyping Implications for practice: Significant advances in genetics and genetic testing requires that NPs be well versed in collecting and interpreting a multigenerational family history to include assessment of the patient/family’s ethnicity/family of origin. The ability to effectively conduct and evaluate the individual’s and family’s health risk through a multigenerational family history will be important in diagnosis, health promotion, disease prevention, and the determination for genetic counseling referral and predictive testing when appropriate. Assessment of risk and prevention of disease is also important in reducing health disparities.
Personal views on the future of entrepreneurship education

Entrepreneurship education is growing worldwide, but key educational and didactical issues remain. What are we talking about when we talk about entrepreneurship education? What are we really doing when we teach or educate people in entrepreneurship, in terms of the nature and the impact of our interventions? What do we know about the appropriateness, the relevancy, the coherency, the social usefulness and the efficiency of our initiatives and practices in entrepreneurship education? Addressing these issues and challenges, this article suggests that at least two major evolutions might reinforce the future of entrepreneurship education. First, we need strong intellectual and conceptual foundations, drawing from the fields of entrepreneurship and education, to strengthen our entrepreneurship courses. And finally, we also need to deeply reflect on our practices, as researchers and educators, taking a more critical stance toward a too often adopted “taken for granted” position.
Online Learning: Stochastic, Constrained, and Smoothed Adversaries

Learning theory has largely focused on two main learning scenarios: the classical statistical setting where instances are drawn i.i. d. from a fixed distribution, and the adversarial scenario wherein, at every time step, an adversarially chosen instance is revealed to the player. It can be argued that in the real world neither of these assumptions is reasonable. We define the minimax value of a game where the adversary is restricted in his moves, capturing stochastic and non-stochastic assumptions on data. Building on the sequential symmetrization approach, we define a notion of distribution-dependent Rademacher complexity for the spectrum of problems ranging from i.i. d. to worst-case. The bounds let us immediately deduce variation-type bounds. We study a smoothed online learning scenario and show that exponentially small amount of noise can make function classes with infinite Littlestone dimension learnable.
Evaluating Saturation Correction Methods for DMSP/OLS Nighttime Light Data: A Case Study from China's Cities

Remotely sensed nighttime lights (NTL) datasets derived from the Defense Meteorological Satellite Program's Operational Linescan System (DMSP/OLS) have been identified as a good indicator of the urbanization process and have been widely used to study such demographic and economic variables as population distribution and density, electricity consumption, and carbon emission. However, one issue must be considered in the application of NTL data, i.e., saturation in the bright cores of urban centers. In this study, we evaluate four correction methods in China's cities: the linear regression model and the cubic regression model at the regional level, and the Human Settlement Index (HSI) and the Vegetation Adjusted NTL Urban Index (VANUI) at a pixel level. The results suggest that both correction methods at the regional level improve the correlation between NTL data and socioeconomic variables. However, since the methods can only be used on saturated pixels, the correction effects are limited, as the saturated area in Chinese cities is rather small. HSI and VANUI increase the inter-urban variability within certain cities,
Fault location methods at compensated MV networks

Major advantages of compensated networks are the self-extinction of arcing faults and that the RMS of the single phase to ground (SPG) fault current is small, and therefore the fault can theoretically be allowed to persist for several hours. The continuous operation of the system can be sustained during a SPG fault in order to continuously supply the consumers if the touch voltage at the poles remains small. A great disadvantage of compensated networks, however, is the complicated way a SPG fault can be located. The first part of this paper contains a short review on problems related to distribution system operators' (DSOs) current practice regarding Earth fault location and sustained faulty operation of compensated networks. Some fault localization methods published in the literature will then be shortly summarized and compared based on computer simulation using EMTP software. Advantages and disadvantages of different methods will be shown. An innovative device and method will be presented that was implemented at two Hungarian DSOs. An evaluation of the operation experience will be given based on real field measurement data. The main contribution of the paper is the proposal for a fault location method that greatly increases system reliability indices and is therefore economically feasible in most distribution systems.
A Novel Reaction Mechanism for the Formation of S-Nitrosothiol in Vivo*

The objective of this study was to investigate the mechanism of S-nitrosothiol formation under physiological conditions. A mechanism is proposed by which nitric oxide (·NO) reacts directly with reduced thiol to produce a radical intermediate, R-S-N·-O-H. This intermediate reduces an electron acceptor to produce S-nitrosothiol. Under aerobic conditions O2 acts as the electron acceptor and is reduced to produce superoxide (O2). The following experimental evidence is provided in support of this mechanism. Cysteine accelerates the consumption of ·NO by 2.5-fold under physiological conditions. The consumption of O2 in the presence of ·NO and cysteine is increased by 2.4-fold. The reaction orders of ·NO and cysteine are second and first order, respectively. The second order of reaction for ·NO may result from interaction between ·NO and O2 to form peroxynitrite. In the presence of Cu,Zn-superoxide dismutase, the reaction of ·NO with cysteine generates hydrogen peroxide, indicating that the reaction generates O2. Finally, the formation of S-nitrosothiol is demonstrated in an anaerobic environment and, as predicted by the mechanism, is dependent on the presence of an electron acceptor. These results demonstrate that under physiological conditions ·NO reacts directly with thiols to form S-nitrosothiol in the presence of an electron acceptor.
Deception, Obedience and Authority

In his article, ‘Milgram's Shocking Experiments’, in Philosophy 52 (1977), Professor Steven C. Patten rejects Milgram's evidence for a Hobbesian view of human nature on three grounds: that the claim that a large number of the subjects in the experiments were not deceived is not convincing, that there is a conceptual conflation by Milgram of two senses of obedience, and that a proper understanding of kinds of authority will explain in an acceptable way the behaviour of most of the small number of subjects who might remain to support Milgram's conclusions. Patten's arguments in support of all three grounds are unsatisfactory.