Miracle-dz/UniFAR-FTUs huggingface dataset:
MICROGLIA ACTIVATION IN A RODENT MODEL OF AN ALCOHOL USE DISORDER: THE IMPORTANCE OF PHENOTYPE, INITIATION, AND DURATION OF ACTIVATION

Chronic ethanol exposure results in neuroadaptations that drive the progression of an alcohol use disorder (AUD). One such driving force is alcohol-induced neurodegeneration. Neuroinflammation has been proposed as a mechanism underlying this damage. Although neuroinflammation is a physiological response to damage, overactivation of its pathways can lead to neurodegeneration. A hallmark indicator of neuroinflammation is microglial activation, but microglial activation is a heterogeneous continuum of phenotypes that can promote or inhibit neuroinflammation. Furthermore acute microglial activation is necessary to restore homeostasis, but prolonged activation can exacerbate damage. The diversity of microglia makes both the level and timecourse of activation vital to understanding their role in damage and/or recovery. The current set of experiments examines the effects of ethanol on microglia within the hippocampus and entorhinal cortex in a binge model of alcohol-induced neurodegeneration. In the first set of experiments, the phenotype of microglia activation was assessed using Raivich’s 5stages of activation that separates proand anti-inflammatory forms of microglia. Morphological and functional assessments suggest that ethanol does not elicit classical microglial activation but instead induces partially activated microglia. In the second set of experiments, the earliest signs of microglial activation were determined to understand the initiation of microglial activation. Experiments indicated that activation occurred subsequent to previous evidence of neuronal damage; however, activation was accompanied by a loss of microglia and the discovery of dystrophic microglia. The final set of experiments examined whether alcohol-induced partial activation of microglia would show a differential response with further alcohol exposure. Experiments showed that animals previously exposed to ethanol showed a greater response to a second ethanol insult. Overall, these studies suggest that although alcohol may initially interrupt the normal microglia response, during abstinence from ethanol a partial activation phenotype appears that may contribute to recovery. Once activated, however, data suggest that these microglia are primed and upon subsequent exposure show an increased response. This heterogeneous microglial response with respect to time does not necessarily reflect a neuroinflammatory response that would be neurodegenerative but does imply that chronic ethanol consumption affects the normal neuroimmune system.
Effects of Gay Identity, Gender and Explicitness of Advertising Imagery on Gay Responses to Advertising

Abstract The present research draws from literature relating to gay identity in psychology and sociology and feminist theory to consider the effect of gay identity and gender on gays' and lesbians' attitudes toward various types of advertising content that are most commonly used to target gay consumers. As such, this study empirically tests whether gay males' and lesbians' responses to gay-oriented advertising content are moderated by individual characteristics: (1) the degree to which they identify as gay, and (2) their gender, and by the explicitness and gender of the gay-oriented advertising imagery.
Atmospheric Chemistry and Physics Discussions Interactive comment on “ Hydrogen isotope fractionation in the photolysis of formaldehyde ”

Commentary on Hydrogen Isotope Fractionation in the Photolysis of Formaldehyde There is clearly a great deal of hard work behind this paper which concerns a critical step in the photochemistry of the atmosphere. I suggest that the paper would be more useful to the readers of ACP if the following points were to be addressed. The terms ’incomplete photolysis’ (R1) and ’complete photolysis’ (R2) are defined in the introduction, referring to the H + HCO and CO + H2 product channels in formaldehyde photolysis respectively. This terminology is confusing, because the experimental procedure relies on the complete photolysis of an HCHO sample to products, presumably involving some amount of both the ’complete’ and ’incomplete’ pathways. These
An Improved High Yield Total Synthesis and Cytotoxicity Study of the Marine Alkaloid Neoamphimedine: An ATP-Competitive Inhibitor of Topoisomerase IIα and Potent Anticancer Agent

Recently, we characterized neoamphimedine (neo) as an ATP-competitive inhibitor of the ATPase domain of human Topoisomerase IIα. Thus far, neo is the only pyridoacridine with this mechanism of action. One limiting factor in the development of neo as a therapeutic agent has been access to sufficient amounts of material for biological testing. Although there are two reported syntheses of neo, both require 12 steps with low overall yields (≤6%). In this article, we report an improved total synthesis of neo achieved in 10 steps with a 25% overall yield. In addition, we report an expanded cytotoxicity study using a panel of human cancer cell lines, including: breast, colorectal, lung, and leukemia. Neo displays potent cytotoxicity (nM IC50 values) in all, with significant potency against colorectal cancer (lowest IC50 = 6 nM). We show that neo is cytotoxic not cytostatic, and that neo exerts cytotoxicity by inducing G2-M cell cycle arrest and apoptosis.
Architectural Exploration of MPSoC Designs Based on an FPGA Emulation Framework

With the growing complexity in consumer embedded products and the improvements in process technology, Multi-Processor System-On-Chip (MPSoC) architectures have become widespread. These new systems are very complex to design as they must execute multiple complex real-time applications (e.g. video processing, or videogames), while meeting several additional design constraints (e.g. energy consumption or time-to-market). Thus, in order to explore all the possible HW-SW configurations in a MPSoC, simulation is not practical anymore due to the large overhead in time of cycle-accurate simulators, which is the desired level for the extraction of statistics. New methods to extract such fine-grained statistics in a faster way are needed. In this paper, we present a new FPGA-based emulation framework that allows designers to rapidly explore a large range of MPSoC design alternatives at the cycle-accurate level. Our experimients using this platform yield a speed-up of three orders of magnitud compared to cycle-accurate MPSoC simulators, while achieving the same level of accuracy as cycle-accurate MPSoC simulation frameworks.
Error and Inference: Frontmatter

Part I. Introduction and Background: 1. Philosophy of methodological practice Deborah Mayo 2. Error statistical philosophy Deborah Mayo and Aris Spanos Part II: 3. Severe testing, error statistics, and the growth of theoretical knowledge Deborah Mayo Part III: 4. Can scientific theories be warranted? Alan Chalmers 5. Can scientific theories be warranted with severity? Exchanges with Alan Chalmers Deborah Mayo Part IV: 6. Critical rationalism, explanation and severe tests Alan Musgrave 7. Towards progressive critical rationalism: exchanges with Alan Musgrave Deborah Mayo Part V: 8. Error, tests and theory-confirmation John Worrall 9. Has Worrall saved his theory (on ad hoc saves) in a non ad hoc manner? Exchanges with Worrall Deborah Mayo Part VI: 10. Mill's sins, or Mayo's errors? Peter Achinstein 11. Sins of the Bayesian epistemologist: exchanges with Achinstein Deborah Mayo Part VII: 12. Theory testing in economics and the error statistical perspective Aris Spanos Part VIII: 13. Frequentist statistics as a theory of inductive inference Deborah Mayo and David Cox 14. Objectivity and conditionality in Frequentist inference David Cox and Deborah Mayo 15. An error in the argument from WCP and S to the SLP Deborah Mayo 16. On a new philosophy of Frequentist inference: exchanges with Cox and Mayo Aris Spanos Part IX: 17. Explanation and truth Clark Glymour 18. Explanation and testing: exchanges with Glymour Deborah Mayo 19. Graphical causal modeling and error statistics: exchanges with Glymour Aris Spanos Part X: 20. Legal epistemology: the anomaly of affirmative defenses Larry Laudan 21. Error and the law: exchanges with Laudan Deborah Mayo.
In ‡ uencing the Misinformed Misbehaver : An Analysis of Public Policy towards Uncertainty and External E ¤ ects ¤

We study a situation in which government in‡uences consumers’ behaviors by providing both information and incentives. We develop the case of consumption choice in the presence of uncertainty and external e¤ects. The instruments used by the government are information campaigns and taxes. A di¢culty arises because the government would like to bolster these less than perfectly e¤ective tools by delivering biased information to the misinformed misbehaver. We study the equilibrium trade-o¤ between informing and o¤ering incentives. Environmental tax policy, anti-smoking campaigns and policy against over-consumption of antibiotics serve as illustrations. Technically we solve a model of signaling cum cheap-talk.
Traffic Aware Energy Efficient Router: Architecture, Prototype and Algorithms

Energy efficient routers are important and promising devices in the roadmap toward green networking. In this paper, we explore this topic with a traffic aware design that can automatically adapt the router's energy consumption to the network traffic in real time with transitions at the scale from microseconds to nanoseconds. In this paper, we make three contributions. First, we propose an energy efficient router architecture using frequency scaling, which is extended from the contemporary line card architecture of the router. Second, we prototype our architecture on a gigabit NetFPGA platform, which extends a router design on that platform to dynamically work at six frequencies. Then, we discuss the implementation in detail and present a per-packet-based power consumption model from real-world measurements. Third, we further propose four algorithms, which efficiently and automatically adapt power grades under the methodology of periodical and threshold-based scaling. Our experiments are carried out on two platforms, a NetFPGA prototype for feasible scenarios and a simulator for other scenarios in excess of the NetFPGA port limit with parameters synthetically generated to the real-world measurement. Experimental results show that approximately 25% power can be saved with our architecture and algorithms. Conclusions are also given to summarize our findings.
A Convex Parametrization of a New Class of Universal Kernel Functions for use in Kernel Learning

We propose a new class of universal kernel functions which admit a linear parametrization using positive semidefinite matrices. These kernels are generalizations of the Sobolev kernel and are defined by piecewise-polynomial functions. The class of kernels is termed "tessellated" as the resulting discriminant is defined piecewise with hyper-rectangular domains whose corners are determined by the training data. The kernels have scalable complexity, but each instance is universal in the sense that its hypothesis space is dense in $L_2$. Using numerical testing, we show that for the soft margin SVM, this class can eliminate the need for Gaussian kernels. Furthermore, we demonstrate that when the ratio of the number of training data to features is high, this method will significantly outperform other kernel learning algorithms. Finally, to reduce the complexity associated with SDP-based kernel learning methods, we use a randomized basis for the positive matrices to integrate with existing multiple kernel learning algorithms such as SimpleMKL.
The Effect of Fatigue on Upper Quarter Y-Balance Test Scores in Recreational Weightlifters: A Randomized Controlled Trial.

BACKGROUND A paucity of research currently exists for upper extremity return to sport testing. The Upper Quarter Y-Balance Test (YBT-UQ) is a clinical test of closed kinetic chain performance with demonstrated reliability. Prior investigations of the YBT-UQ were conducted with individuals in a resting state and no comparison to performance in a fatigued state has been conducted. PURPOSE To examine the effect of upper extremity fatigue on the performance of the YBT-UQ in recreational weightlifters. STUDY DESIGN Randomized controlled trial. METHODS 24 participants who participated in recreational weight training three days per week were randomly allocated to a control or experimental group. Individuals in the control group were tested using the YBT-UQ and re-tested after a 20-minute rest period. Participants in the experimental group were tested with the YBT-UQ, performed an upper extremity exercise fatigue protocol, and immediately re-tested. Examiners were blinded to participant allocation. RESULTS Differences from pre- to post-fatigue YBT-UQ testing revealed score reductions between 2.04cm - 12.16cm for both composite scores and individual reach directions. The repeated measures ANOVA revealed significant differences when comparing the pre- and post-testing results between the fatigue and non-fatigue groups for all individual directions (p ≤ .006) and composite scores both limbs (p<.035). CONCLUSION The performance of an upper body fatigue protocol significantly reduces YBT-UQ scores in recreational weightlifters. LEVEL OF EVIDENCE 1b.
AtOPT3, a Member of the Oligopeptide Transporter Family, Is Essential for Embryo Development in Arabidopsis

A T-DNA–tagged population of Arabidopsis was screened for mutations in AtOPT3, which encodes a member of the oligopeptide (OPT) family of peptide transporters, and a recessive mutant allele, opt3, was identified. Phenotypic analysis of opt3 showed that most homozygous embryos were arrested at or before the octant stage of embryo development and that none showed the usual periclinal division leading to the formation of the protoderm. This defective phenotype could be reversed by complementation with the full-length, wild-type AtOPT3 gene. A β-glucuronidase (GUS) fusion to DNA sequences upstream of the putative AtOPT3 ATG start codon was constructed, and the expression pattern was assayed in transgenic plants. AtOPT3 was expressed in the vascular tissues of seedlings and mature plants as well as in pollen. Consistent with the function of AtOPT3 in embryogenesis, AtOPT3::GUS expression also was detected in developing embryos and in the maternal tissues of seeds. These data suggest a critical role for peptide transport in early embryo development.
Conspecific sperm precedence in Callosobruchus subinnotatus (Coleoptera: Bruchidae): mechanisms and consequences

Conspecific sperm precedence (CSP) has been identified as an important post-copulatory, pre-zygotic mechanism that can act to reduce gene flow between populations. The evolution of CSP is thought to have arisen as a by-product of male and female coevolution in response to intraspecific post-copulatory sexual selection. However, little is known about the mechanisms that generate CSP. When Callosobruchus subinnotatus females copulate with both C. subinnotatus and Callosobruchus maculatus males, regardless of mating order, the majority of eggs are fertilized by conspecific sperm. The low number of heterospecific fertilizations does not result from general differences in the viability of sperm in the female reproductive tract, as heterospecific sperm fertilized equivalent numbers of eggs as conspecific sperm in the absence of sperm competition. Instead, CSP results from disadvantages to heterospecific sperm that are manifest only when in competition with conspecific sperm. CSP in C. subinnotatus appears to result from two, not mutually exclusive, mechanisms. First, conspecific sperm are better able to displace heterospecific sperm from female storage. Second, conspecific sperm achieve disproportionately higher numbers of fertilizations relative to their proportional representation in the fertilization set. Thus, we provide evidence of differential sperm use from the female spermatheca.
Functional Neuroanatomy of the Cognitive Process of Mapping During Discourse Comprehension

We used functional magnetic resonance imaging (fMRI) to identify brain regions involved in the process of mapping coherent discourse onto a developing mental representation. We manipulated discourse coherence by presenting sentences with definite articles (which lead to more coherent discourse) or indefinite articles (which lead to less coherent discourse). Comprehending connected discourse, compared with reading unrelated sentences, produced more neural activity in the right than left hemisphere of the frontal lobe. Thus, the right hemisphere of the frontal lobe is involved in some of the processes underlying mapping. In contrast, left-hemisphere structures were associated with lower-level processes in reading (such as word recognition and syntactic processing). Our results demonstrate the utility of using fMRI to investigate the neural substrates of higher-level cognitive processes such as discourse comprehension.
Celiac Disease in Patients With HCV Genotype 1A

TO THE EDITOR: A 70-yr-old man treated with interferon 2b (INF 2b) for chronic hepatitis C presented with acute rhabdomyolysis. Hepatitis C was diagnosed 6 months previously (confirmed by results of polymerase chain reaction), and liver biopsy showed moderate chronic hepatitis (histological activity index (HAI) 15, fibrosis 2) (1). Treatment with INF 2b (3 MIU three times wk) was started. Two weeks later, he was referred to our unit of Internal Medicine for sudden appearance of fever (38°C), weakness, and acute generalized myalgia. On admission, he denied any antecedent signs of infection, any trauma, and assumption of any other drugs except for INF. General physical examination resulted normal. Laboratory findings showed a marked increase in the concentrations of creatine kinase at 3.641 U/L (normal range 5–70 U/L) with normal concentrations of the isoform creatine kinase-MB (CK-MB), lactate dehydrogenase at 717 U/L (normal range 80–240 U/L). Myoglobinuria was present (88 mg/L). There were no pathological alterations in concentrations of creatinine, urea nitrogen, C-reactive protein, blood cell counts, or glucose. No electrolyte abnormalities were detectable. With the diagnosis of rhabdomyolysis, INF 2b treatment was discontinued. The patient was treated with i.v. fluids and bicarbonate to maintain an alkaline urine output. Within 4 days, fever and myalgia disappeared, and weakness significantly improved; the creatine kinase declined to normal values (101 U/L). At the follow-up visit at 2 and 4 months, the patient was in good condition, and creatine kinase was within the normal range. Rhabdomyolysis has been reported as an unusual adverse reaction to several drugs, in particular in patients treated with statin (2). A few cases of acute rhabdomyolysis associated with INF 2b have been reported. Greenfield et al. described a patient 10 wk after initiation of INF 2b treatment starting with 5 MU three times/wk for chronic active hepatitis C (3). Reinhold et al. recently described a fatal outcome of fulminant rhabdomyolysis with multiple organ failure in a 56-yr-old man receiving adjuvant high-dose INF 2b (20 Mio. 1E m 2 daily) (4). The authors revealed that the manufacturers of INF 2b have received only 11 reports worldwide. Remarkably, the manifestation of muscle injury occurred when the dose of INF 2b was being increased in both patients described, suggesting that rhabdomyolysis represents at least a dose-dependent side effect of this drug. With respect to the previous reports, in our patient, the dosage of INF 2b was unaltered and significantly lower; moreover, the clinical and laboratory alterations were milder, and the recovery of the patient was quite quicker. These findings seem to confirm that muscle injury could be (if rare) a side effect of INF 2b, and to suggest that it may occur also at low doses. INF 2b discontinuation leads to a complete recovery of the disease. Measurement of creatine kinase activity could be recommended after initiation of INF 2b treatment and after every increasing of its dosage to precociously individualize and prevent irreversible rhabdomyolysis.
Evaluation of the DDSolver Software Applications

When a new oral dosage form is developed, its dissolution behavior must be quantitatively analyzed. Dissolution analysis involves a comparison of the dissolution profiles and the application of mathematical models to describe the drug release pattern. This report aims to assess the application of the DDSolver, an Excel add-in software package, which is designed to analyze data obtained from dissolution experiments. The data used in this report were chosen from two dissolution studies. The results of the DDSolver analysis were compared with those obtained using an Excel worksheet. The comparisons among three different products obtained similarity factors (f 2) of 23.21, 46.66, and 17.91 using both DDSolver and the Excel worksheet. The results differed when DDSolver and Excel were used to calculate the release exponent “n” in the Korsmeyer-Peppas model. Performing routine quantitative analysis proved to be much easier using the DDSolver program than an Excel spreadsheet. The use of the DDSolver program reduced the calculation time and has the potential to omit calculation errors, thus making this software package a convenient tool for dissolution comparison.
Activation of NAD(P)H Oxidase by Tryptophan-Derived 3-Hydroxykynurenine Accelerates Endothelial Apoptosis and Dysfunction In Vivo

Rationale: The kynurenine (Kyn) pathway is the major route for tryptophan (Trp) metabolism in mammals. The Trp–Kyn pathway is reported to regulate several fundamental biological processes, including cell death. Objective: The aim of this study was to elucidate the contributions and molecular mechanism of Trp–Kyn pathway to endothelial cell death. Methods and Results: Endogenous reactive oxygen species, endothelial cell apoptosis, and endothelium-dependent and endothelium-independent vasorelaxation were measured in aortas of wild-type mice or mice deficient for nicotinamide adenine dinucleotide phosphate [NAD(P)H] oxidase subunits (p47phox or gp91phox) or indoleamine-pyrrole 2,3-dioxygenase 1 with or without angiotensin (Ang) II infusion. As expected, AngII increased plasma levels of Kyn- and 3-hydroxykynurenine–modified proteins in endothelial cells in vivo. Consistent with this, AngII markedly increased the expression of indoleamine-pyrrole 2,3-dioxygenase in parallel with increased expression of interferon-&ggr;. Furthermore, in wild-type mice, AngII significantly increased oxidative stress, endothelial cell apoptosis, and endothelial dysfunction. These effects of AngII infusion were significantly suppressed in mice deficient for p47phox, gp91phox, or indoleamine-pyrrole 2,3-dioxygenase 1, suggesting that AngII-induced enhancement of Kynurenines via NAD(P)H oxidase–derived oxidants causes endothelial cell apoptosis and dysfunction in vivo. Furthermore, interferon-&ggr; neutralization eliminates AngII-increased superoxide products and endothelial apoptosis by inhibiting AngII-induced Kynurenines generation, suggesting that AngII-activated Kyn pathway is interferon-&ggr;–dependent. Mechanistically, we found that AngII-enhanced 3-hydroxykynurenine promoted the generation of NAD(P)H oxidase–mediated superoxide anions by increasing the translocation and membrane assembly of NAD(P)H oxidase subunits in endothelial cells, resulting in accelerated apoptosis and consequent endothelial dysfunction. Conclusions: Kyn pathway activation accelerates apoptosis and dysfunction of the endothelium by upregulating NAD(P)H-derived superoxide.