Miracle-dz/UniFAR-FTUs huggingface dataset:
Death Receptor-Induced Activation of Initiator Caspase 8 Is Antagonized by Serine/Threonine Kinase PAK4

ABSTRACT Normal cell growth requires a precisely controlled balance between cell death and survival. This involves activation of different types of intracellular signaling cascades within the cell. While some types of signaling proteins regulate apoptosis, or programmed cell death, other proteins within the cell can promote survival. The serine/threonine kinase PAK4 can protect cells from apoptosis in response to several different types of stimuli. As is the case for other members of the p21-activated kinase (PAK) family, one way that PAK4 may promote cell survival is by phosphorylating and thereby inhibiting the proapoptotic protein Bad. This leads in turn to the inhibition of effector caspases such as caspase 3. Here we show that in response to cytokines which activate death domain-containing receptors, such as the tumor necrosis factor and Fas receptors, PAK4 can inhibit the death signal by a different mechanism. Under these conditions, PAK4 inhibits apoptosis early in the caspase cascade, antagonizing the activation of initiator caspase 8. This inhibition, which does not require PAK4's kinase activity, may involve inhibition of caspase 8 recruitment to the death domain receptors. This role in regulating initiator caspases is an entirely novel role for the PAK proteins and suggests a new mechanism by which these proteins promote cell survival.
Mutational reconstructed ferric chelate reductase confers enhanced tolerance in rice to iron deficiency in calcareous soil

Iron (Fe) deficiency is a worldwide agricultural problem on calcareous soils with low-Fe availability due to high soil pH. Rice plants use a well documented phytosiderophore-based system (Strategy II) to take up Fe from the soil and also possess a direct Fe2+ transport system. Rice plants are extremely susceptible to low-Fe supply, however, because of low phytosiderophore secretion and low Fe3+ reduction activity. A yeast Fe3+ chelate-reductase gene refre1/372, selected for better performance at high pH, was fused to the promoter of the Fe-regulated transporter, OsIRT1, and introduced into rice plants. The transgene was expressed in response to a low-Fe nutritional status in roots of transformants. Transgenic rice plants expressing the refre1/372 gene showed higher Fe3+ chelate-reductase activity and a higher Fe-uptake rate than vector controls under Fe-deficient conditions. Consequently, transgenic rice plants exhibited an enhanced tolerance to low-Fe availability and 7.9× the grain yield of nontransformed plants in calcareous soils. This report shows that enhancing the Fe3+ chelate-reductase activity of rice plants that normally have low endogenous levels confers resistance to Fe deficiency.
Selecting Forwarding Neighbors in Wireless Ad Hoc Networks

Broadcasting is a fundamental operation which is frequent in wireless ad hoc networks. A simple broadcasting mechanism, known as flooding, is to let every node retransmit the message to all its 1-hop neighbors when receiving the first copy of the message. Despite its simplicity, flooding is very inefficient and can result in high redundancy, contention, and collision. One approach to reducing the redundancy is to let each node forward the message only to a small subset of 1-hop neighbors that cover all of the node's 2-hop neighbors. In this paper we propose two practical heuristics for selecting the minimum number of forwarding neighbors: an O(nlog n) time algorithm that selects at most 6 times more forwarding neighbors than the optimum, and an O(nlog 2n) time algorithm with an improved approximation ratio of 3, where n is the number of 1- and 2-hop neighbors. The best previously known algorithm, due to Bronnimann and Goodrich [2], guarantees O(1) approximation in O(n3 log n) time.
Design technique for class E RF/MW amplifiers with linear equivalent of transistor's output capacitance

In class E amplifiers the nonlinear output capacitance of the device often reaches, or even exceeds the necessary value given by classical analysis in RF applications. The 100-percent efficiency condition imposes a constraint on the maximum susceptance value of the shunting capacitor consequently limiting the maximum frequency of the stage. In order to easily incorporate this nonlinear capacitance to the analysis and design of class E amplifiers, this paper addresses the use of a linear equivalent of a transistor nonlinear voltage-dependent output capacitance. The EQUIVALENT [Mediano, 2000] concept as well as a FORM FACTOR [Mediano, 2000] representing the quotient of the nonlinear capacitance to the linear theoretical case are used. Other important consequences affecting the normalization, design procedure and frequency scheme of class E amplifiers are also presented.
Clinical and Molecular Characterization of Patients With Catecholaminergic Polymorphic Ventricular Tachycardia

Background—Mutations in the cardiac ryanodine receptor gene (RyR2) underlie catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited arrhythmogenic disease occurring in the structurally intact heart. The proportion of patients with CPVT carrying RyR2 mutations is unknown, and the clinical features of RyR2-CPVT as compared with nongenotyped CPVT are undefined. Methods and Results—Patients with documented polymorphic ventricular arrhythmias occurring during physical or emotional stress with a normal heart entered the study. The clinical phenotype of the 30 probands and of 118 family members was evaluated, and mutation screening on the RyR2 gene was performed. Arrhythmias documented in probands were: 14 of 30 bidirectional ventricular tachycardia, 12 of 30 polymorphic ventricular tachycardia, and 4 of 30 catecholaminergic idiopathic ventricular fibrillation;RyR2 mutations were identified in 14 of 30 probands (36% bidirectional ventricular tachycardia, 58% polymorphic ventricular tachycardia, 50% catecholaminergic idiopathic ventricular fibrillation) and in 9 family members (4 silent gene carriers). Genotype-phenotype analysis showed that patients with RyR2 CPVT have events at a younger age than do patients with nongenotyped CPVT and that male sex is a risk factor for syncope in RyR2-CPVT (relative risk=4.2). Conclusions—CPVT is a clinically and genetically heterogeneous disease manifesting beyond pediatric age with a spectrum of polymorphic arrhythmias. &bgr;-Blockers reduce arrhythmias, but in 30% of patients an implantable defibrillator may be required. Genetic analysis identifies two groups of patients: Patients with nongenotyped CPVT are predominantly women and become symptomatic later in life; patients with RyR2 CPVT become symptomatic earlier, and men are at higher risk of cardiac events. These data provide a rationale for prompt evaluation and treatment of young men with RyR2 mutations.
The hemodynamic effects of anesthetic induction in vascular surgical patients chronically treated with angiotensin II receptor antagonists.

UNLABELLED The use of angiotensin II receptor subtype-1 antagonists (ARA), recently introduced as antihypertensive drugs, is becoming more prevalent. We studied the prevalence and severity of hypotension after the induction of general anesthesia in 12 patients treated with ARA until the morning of surgery. The hemodynamic response to induction was compared with that of patients treated with beta-adrenergic blockers (BB) and/or calcium channel blockers (CB) (BB/CB group, n = 45) and angiotensin-converting enzyme inhibitors (ACEI) (ACEI group, n = 27). A standardized anesthesia induction protocol was followed for all patients. Hypotension occurred significantly (p < or = 0.05) more often in ARA-treated patients (12 of 12) compared with BB/CB-treated patients (27 of 45) or with ACEI-treated patients (18 of 27). There was a significantly (P < or = 0.001) increased ephedrine requirement in the ARA group (21+/-3 mg) compared with the BB/CB group (10+/-6 mg) or the ACEI group (7+/-4 mg). Hypotension refractory to repeated ephedrine or phenylephrine administration occurred significantly (P < or = 0.05) more in the ARA group (4 of 12) compared with the BB/CB group (0 of 45) or the ACEI group (1 of 27), but it was treated successfully by using a vasopressin system agonist. Treatment with angiotensin II antagonism until the day of surgery is associated with severe hypotension after the induction of anesthesia, which, in some cases, can only be treated with an agonist of the vasopressin system. IMPLICATIONS Hypotensive episodes occur more frequently after anesthetic induction in patients receiving Angiotensin II receptor subtype-1 antagonists under anesthesia than with other hypotensive drugs. They are less responsive to the vasopressors ephedrine and phenylephrine. The use of a vasopressin system agonist was effective in restoring blood pressure when hypotension was refractory to conventional therapy.
Biochemical novelty in Tragopogon : a paradigm for understanding the ‘ success ’ of polyploids

Nearly four decades ago, Roose & Gottlieb (Roose & Gottlieb 1976 Evolution 30, 818–830. (doi:10.2307/2407821)) showed that the recently derived allotetraploids Tragopogon mirus and T. miscellus combined the allozyme profiles of their diploid parents (T. dubius and T. porrifolius, and T. dubius and T. pratensis, respectively). This classic paper addressed the link between genotype and biochemical phenotype and documented enzyme additivity in allopolyploids. Perhaps more important than their model of additivity, however, was their demonstration of novelty at the biochemical level. Enzyme multiplicity—the production of novel enzyme forms in the allopolyploids—can provide an extensive array of polymorphism for a polyploid individual and may explain, for example, the expanded ranges of polyploids relative to their diploid progenitors. In this paper, we extend the concept of evolutionary novelty in allopolyploids to a range of genetic and ecological features. We observe that the dynamic nature of polyploid genomes—with alterations in gene content, gene number, gene arrangement, gene expression and transposon activity— may generate sufficient novelty that every individual in a polyploid population or species may be unique. Whereas certain combinations of these features will undoubtedly be maladaptive, some unique combinations of newly generated variation may provide tremendous evolutionary potential and adaptive capabilities.
VLSI Architecture for the Low-Computation Cycle and Power-Efficient Recursive DFT/IDFT Design

In this paper, we propose one low-computation cycle and power-efficient recursive discrete Fourier transform (DFT)/inverse DFT (IDFT) architecture adopting a hybrid of input strength reduction, the Chebyshev polynomial, and register-splitting schemes. Comparing with the existing recursive DFT/IDFT architectures, the proposed recursive architecture achieves a reduction in computation-cycle by half. Appling this novel low-computation cycle architecture, we could double the throughput rate and the channel density without increasing the operating frequency for the dual tone multi-frequency (DTMF) detector in the high channel density voice over packet (VoP) application. From the chip implementation results, the proposed architecture is capable of processing over 128 channels and each channel consumes 9.77 μW under 1.2 [email protected] in TSMC 0.13 1P8M CMOS process. The proposed VLSI implementation shows the power-efficient advantage by the low-computation cycle architecture.
Step rate-determined walking intensity and walking recommendation in Chinese young adults: a cross-sectional study

Abstract There is lack of data on the physiological characteristics of over ground walking and walking recommendations for Chinese young adult. The purpose of the study was to measure walking-related energy expenditure during field testing, to identify step-rate cut-point associated with moderate and vigorous intensity, and to translate physical activity (PA) guidelines into walking goals for Chinese young adults. Design Cross-sectional analytic study. Setting Two communities from Beijing and Shanghai in China. Participants A sample of 226 Chinese adults (117 men, 109 women) with a mean age of 21.7 (±0.2) years, volunteered to participate in the study. All Participants were recreationally active without orthopaedic limitations, free of chronic diseases, not taking any medications that affect metabolism and non-smokers. Outcome measures All the participants completed four 6 minincremental over ground walking at different speeds of 3.8, 4.8, 5.6 and 6.4 km/h, respectively. Indirect calorimeter was used to measure energy expenditure at each speed. Receiver operating characteristic curves were used to determine the step-rate cut-points associated with moderate and vigorous intensity activity. Results At the same walking speed, step counts per minute were higher in women than in men. No significant differences were found in VO2 per weight (ml/kg/min) between women and men. Step-rate cut-point associated with walking at 3 metabolic equivalents (METs) and 6METs were 105 and 130 step/min when analysing men and women together. There were slight differences on the cut-points between women and men if data were analysed separately. Conclusions In order to meet PA guidelines, Chinese young adult should walk 30 min with at least 105 step/min or 3150 steps or 2 km with the same step-rate per day. Walking at a higher speed of 130 step/min might provide additional health benefit.
The Effects of Background Noise on the Neural Responses to Natural Sounds in Cat Primary Auditory Cortex

Animal vocalizations in natural settings are invariably accompanied by an acoustic background with a complex statistical structure. We have previously demonstrated that neuronal responses in primary auditory cortex of halothane-anesthetized cats depend strongly on the natural background. Here, we study in detail the neuronal responses to the background sounds and their relationships to the responses to the foreground sounds. Natural bird chirps as well as modifications of these chirps were used. The chirps were decomposed into three components: the clean chirps, their echoes, and the background noise. The last two were weaker than the clean chirp by 13 and 29 dB on average respectively. The test stimuli consisted of the full natural stimulus, the three basic components, and their three pairwise combinations. When the level of the background components (echoes and background noise) presented alone was sufficiently loud to evoke neuronal activity, these background components had an unexpectedly strong effect on the responses of the neurons to the main bird chirp. In particular, the responses to the original chirps were more similar on average to the responses evoked by the two background components than to the responses evoked by the clean chirp, both in terms of the evoked spike count and in terms of the temporal pattern of the responses. These results suggest that some of the neurons responded specifically to the acoustic background even when presented together with the substantially louder main chirp, and may imply that neurons in A1 already participate in auditory source segregation.
Preparation and properties of recombinant DNA derived tobacco mosaic virus coat protein.

Recombinant DNA derived tobacco mosaic virus (vulgare strain) coat protein (r-TMVP) was obtained by cloning and expression in Escherichia coli and was purified by column chromatography, self-assembly polymerization, and precipitation. SDS-PAGE, amino terminal sequencing, and immunoblotting with polyclonal antibodies raised against TMVP confirmed the identify and purity of the recombinant protein. Isoelectric focusing in 8 M urea and fast atom bombardment mass spectrometry demonstrated that the r-TMVP is not acetylated at the amino terminus, unlike the wild-type protein isolated from the tobacco plant derived virus. The characterization of r-TMVP with regard to its self-assembly properties revealed reversible endothermic polymerization as studied by analytical ultracentrifugation, circular dichroism, and electron microscopy. However, the details of the assembly process differed from those of the wild-type protein. At neutral pH, low ionic strength, and 20 degrees C, TMVP forms a 20S two-turn helical rod that acts as a nucleus for further assembly with RNA and additional TMVP to form TMV. Under more acidic conditions, this 20S structure also acts as a nucleus for protein self-assembly to form viruslike RNA-free rods. The r-TMVP that is not acetylated carries an extra positive charge at the amino terminus and does not appear to form the 20S nucleus. Instead, it forms a 28S four-layer structure, which resembles in size and structure the dimer of the bilayer disk formed by the wild-type protein at pH 8.0, high ionic strength, and 20 degrees C. (ABSTRACT TRUNCATED AT 250 WORDS)
Protective Effect of Resveratrol against IL-1β-Induced Inflammatory Response on Human Osteoarthritic Chondrocytes Partly via the TLR4/MyD88/NF-κB Signaling Pathway: An “in Vitro Study”

Resveratrol is a natural polyphenolic compound that prevents inflammation in chondrocytes and animal models of osteoarthritis (OA) via yet to be defined mechanisms. The purpose of this study was to determine whether the protective effect of resveratrol on IL-1β-induced human articular chondrocytes was associated with the TLR4/MyD88/NF-κB signaling pathway by incubating human articular chondrocytes (harvested from osteoarthritis patients) with IL-1β before treatment with resveratrol. Cell viability was evaluated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and TNFα levels in culture supernatants were measured by ELISA(Enzymelinked immunosorbent assay). The levels of TLR4 and its downstream signaling targets (MyD88 and TRAF6) and IL-1β were assessed by measuring the levels of mRNA and protein expression by real-time RT-PCR and western blot analysis, respectively, in addition to assessing NF-κB activation. In addition, TLR4 siRNA was used to block TLR4 expression in chondrocytes further demonstrating that resveratrol prevented IL-1β-mediated inflammation by TLR4 inhibition. We found that resveratrol prevented IL-1β-induced reduction in cell viability. Stimulation of chondrocytes with IL-1β caused a significant up-regulation of TLR4 and its downstream targets MyD88 and TRAF6 resulting in NF-κB activation associated with the synthesis of IL-1β and TNFα. These IL-1β-induced inflammatory responses were all effectively reversed by resveratrol. Furthermore, activation of NF-κB in chondrocytes treated with TLR4 siRNA was significantly attenuated, but not abolished, and exposure to resveratrol further reduced NF-κB translocation. These data suggested that resveratrol prevented IL-1β-induced inflammation in human articular chondrocytes at least in part by inhibiting the TLR4/MyD88/NF-κB signaling pathway suggesting that resveratrol has the potential to be used as a nutritional supplement to counteract OA symptoms.
How the US drug safety system should be changed.

READING A RECENT NEWSPAPER MIGHT REMIND ONE of the above quote. One of the questions the nation is currently confronted with is what should be done to address the safety of drugs. In this Commentary, the current system of drug safety monitoring will be described and the limitations of the current system will be highlighted. A potential solution will then be proposed that will require legislation to implement.
Induction Programs That Keep New Teachers Teaching and Improving

This article features schools and school districts with successful induction programs, all easily replicable. Increasingly, research confirms that teacher and teaching quality are the most powerful predictors of student success. In short, principals ensure higher student achievement by assuring better teaching. To do this, effective administrators have a new teacher induction program available for all newly hired teachers, which then seamlessly becomes part of the lifelong, sustained professional development program for the district or school. What keeps a good teacher are structured, sustained, intensive professional development programs that allow new teachers to observe others, to be observed by others, and to be part of networks or study groups where all teachers share together, grow together, and learn to respect each other's work.
Does the Source Matter in the Communication of Anti-Smoking Messages to Youth?

This study examined ethnicity as a moderator of exposure to sources of anti-smoking communication and behavioral intentions among adolescents who have never tried smoking (i.e., never smokers) and those who previously experimented with smoking but are not yet regular smokers (i.e., experimental smokers). Responses from 1700 African American, Latino, and White youth who completed the Virginia Youth Tobacco Survey from September 2007 through April 2008 were analyzed. Ethnicity and smoking status moderated the association between exposure to sources of anti-tobacco communication and adolescents' intentions to smoke. For never smokers, media exposure was related to lower behavioral intentions among African Americans. For experimental smokers, exposure to both media and to health professionals was associated with lower intentions among African Americans. Exposure to parental anti-smoking communication was associated with reduced intentions among White adolescents. These findings suggest that prevention for smoking initiation among ethnically diverse youth might be enhanced with greater attention to the source of anti-smoking messages and prior smoking experience.
Challenges for management development in the German‐speaking nations for the twenty‐first century

Close inspection reveals subtle differences in managerial style and culture within Austria, Germany and Switzerland. Foreign management development (MD) practitioners are more likely to be impressed by the management and cultural similarities within the German‐speaking nations, especially when contrasted with the North American model. While many of the MD techniques used in the German‐speaking areas will be familiar to North American practitioners, not all foreign MD techniques are directly applicable to management in the German‐speaking region. Nonetheless, these countries face familiar challenges in developing managers into the twenty‐first century. These countries need managers who can cope with rapid change, manage innovation and new technologies, develop their human resource and management skills, face globalisation, deal with information technology, as well as manage teams and external workforces. Many of these areas offer opportunities for foreign MD practitioners. Promoting intercultural development could be a strong argument for exposing German‐nation managers to foreign MDPs
Endocrine control of metabolic adaptation during lactation

This topic has been the subject of a number of recent reviews (e.g., Bauman & Elliot, 1983; Collier et al. 1984; Forsyth, 1986; Williamson, 1986; Girard et al. 1987; Vernon, 1988). In this brief essay I have therefore focused mainly on recent developments, especially in changes in endocrine responsiveness of tissues with lactation. In addition, I have tried to highlight some of the important differences and similarities between domestic ruminants and laboratory rodents in their metabolic adaptations and their endocrine control during lactation.
Interplay of the iron-regulated metastasis suppressor NDRG1 with epidermal growth factor receptor (EGFR) and oncogenic signaling

The iron-regulated metastasis suppressor N-myc downstream-regulated gene 1 (NDRG1) has been shown to inhibit numerous oncogenic signaling pathways in cancer cells. Recent findings have demonstrated that NDRG1 inhibits the ErbB family of receptors, which function as key inducers of carcinogenesis. NDRG1 attenuates ErbB signaling by inhibiting formation of epidermal growth factor receptor (EGFR)/human epidermal growth factor receptor 2 (HER2) and HER2/HER3 heterodimers and by down-regulating EGFR via a mechanism involving its degradation. Understanding the complex interplay between NDRG1, iron, and ErbB signaling is vital for identifying novel, more effective targets for cancer therapy.