Miracle-dz/UniFAR-FTUs huggingface dataset:
The Mechanism of Ran Import into the Nucleus by Nuclear Transport Factor 2*

The small GTPase Ran is essential for virtually all nucleocytoplasmic transport events. It is hypothesized that Ran drives vectorial transport of macromolecules into and out of the nucleus via the establishment of a Ran gradient between the cytoplasm and nucleoplasm. Although Ran shuttles between the nucleus and cytoplasm, it is concentrated in the nucleus at steady state. We show that nuclear transport factor 2 (NTF2) is required to concentrate Ran in the nucleus in the budding yeast, Saccharomyces cerevisiae. To analyze the mechanism of Ran import into the nucleus by NTF2, we use mutants in a variety of nuclear transport factors along with biochemical analyses of NTF2 complexes. We find that Ran remains concentrated in the nucleus when importin-mediated protein import is disrupted and demonstrate that NTF2 does not form a stable complex with the transport receptor, importin-β. Consistent with a critical role for NTF2 in establishing and maintaining the Ran gradient, we show that NTF2 is required for early embryogenesis inCaenorhabditis elegans. Our data distinguish between two possible mechanisms for Ran import by NTF2 and demonstrate that Ran import is independent from importin-β-mediated protein import.
Role of the LytSR Two-Component Regulatory System in Adaptation to Cationic Antimicrobial Peptides in Staphylococcus aureus

ABSTRACT Many host defense cationic antimicrobial peptides (HDPs) perturb the staphylococcal cell membrane (CM) and alter transmembrane potential (ΔΨ) as key parts of their lethal mechanism. Thus, a sense-response system for detecting and mediating adaptive responses to such stresses could impact organism survival; the Staphylococcus aureus LytSR two-component regulatory system (TCRS) may serve as such a ΔΨ sensor. One well-known target of this system is the lrgAB operon, which, along with the related cidABC operon, has been shown to be a regulator in the control of programmed cell death and lysis. We used an isogenic set of S. aureus strains: (i) UAMS-1, (ii) its isogenic ΔlytS and ΔlrgAB mutants, and (iii) plasmid-complemented ΔlytSR and ΔlrgAB mutants. The ΔlytS strain displayed significantly increased in vitro susceptibilities to all HDPs tested (neutrophil-derived human neutrophil peptide 1 [hNP-1], platelet-derived thrombin-induced platelet microbicidal proteins [tPMPs], and the tPMP-mimetic peptide RP-1), as well as to calcium-daptomycin (DAP), a cationic antimicrobial peptide (CAP). In contrast, the ΔlrgAB strain exhibited no significant changes in susceptibilities to these cationic peptides, indicating that although lytSR positively regulates transcription of lrgAB, increased HDP/CAP susceptibilities in the ΔlytS mutant were lrgAB independent. Further, parental UAMS-1 (but not the ΔlytS mutant) became more resistant to hNP-1 and DAP following pretreatment with carbonyl cyanide m-chlorophenylhydrazone (CCCP) (a CM-depolarizing agent). Of note, lytSR-dependent survival against CAP/HDP killing was not associated with changes in either surface positive charge, expression of mprF and dlt, or CM fluidity. The ΔlytS strain (but not the ΔlrgAB mutant) displayed a significant reduction in target tissue survival in an endocarditis model during DAP treatment. Collectively, these results suggest that the lytSR TCRS plays an important role in adaptive responses of S. aureus to CM-perturbing HDPs/CAPs, likely by functioning as a sense-response system for detecting subtle changes in ΔΨ.
Conformational dynamics of helix S6 from Shaker potassium channel: simulation studies.

Prolines in transmembrane (TM) alpha-helices are believed to play an important structural and/or functional role in membrane proteins. At a structural level a proline residue distorts alpha-helical structure due to the loss of at least one stabilizing backbone hydrogen bond, and introduces flexibility in the helix that may result in substantial kink and swivel motions about the effective "hinge. " At a functional level, for example in Kv channels, it is believed that proline-induced molecular hinges may have a direct role in gating, i.e., the conformational change linked to opening/closing the channel to movement of ions. In this article we study the conformational dynamics of the S6 TM helix from of the Kv channel Shaker, which possesses the motif PVP--a motif that is conserved in Kv channels. We perform multiple molecular dynamics simulations of single S6 helices in a membrane-mimetic environment in order to effectively map the kink-swivel conformational space of the protein, exploiting the ability of multiple simulations to achieve greater sampling. We show that the presence of proline locally perturbs the helix, disrupting local dihedral angles and producing local twist and unwinding in the region of the hinge--an effect that is relaxed with distance from the PVP motif. We furthermore show that motions about the hinge are highly anisotropic, reflecting a preferred region of kink-swivel conformation space that may have implications for the gating process.
TIM‐3 is expressed on activated human CD4+ T cells and regulates Th1 and Th17 cytokines

TIM‐3 is a molecule selectively expressed on a subset of murine IFN‐γ‐secreting T helper 1 (Th1) cells but not Th2 cells, and regulates Th1 immunity and tolerance in vivo. At this time little is known about the role of TIM‐3 on human T cells. To determine if TIM‐3 similarly identifies and regulates Th1 cells in humans, we generated a panel of mAb specific for human TIM‐3. We report that TIM‐3 is expressed by a subset of activated CD4+ cells, and that anti‐CD3/anti‐CD28 stimulation increases both the level of expression as well as the number of TIM‐3+ T cells. We also find that TIM‐3 is expressed at high levels on in vitro polarized Th1 cells, and is expressed at lower levels on Th17 cells. In addition, human CD4+ T cells secreted elevated levels of IFN‐γ, IL‐17, IL‐2, and IL‐6, but not IL‐10, IL‐4, or TNF‐α, when stimulated with anti‐CD3/anti‐CD28 in the presence of TIM‐3‐specific, putative antagonistic antibodies. This was not mediated by differences in proliferation or cell death, but rather by induction of cytokines at the transcriptional level. These results suggest that TIM‐3 is a negative regulator of human T cells and regulates Th1 and Th17 cytokine secretion.
Mouth care and skin care in palliative medicine

EDITOR—We advocated a pragmatic approach to mouth and skin care in the ABC of Palliative Care.1 Not all the suggestions in the subsequent correspondence followed the same principle.2 Lucas and Roberts rightly point to the evidence for chlorhexidine in reducing oral bacteria. They fail to point out that chlorhexidine alters taste and can damage oral mucosa and that some randomised trials have shown it to be no better than water in preventing mucositis caused by treatments …
A relevance vector machine-based approach for remaining useful life prediction of power MOSFETs

Accurate prediction of the RUL (remaining useful life) of a degradation component is crucial to the PHM for an electronic system. Power MOSFETs are widely used as essential components of electronic and electrical subsystems and its degradation has got more and more attention. This paper introduces a prognostic method which based on relevance vector machine and a degradation model to predict the RUL of power MOSFET. The proposed method uses relevance vector machine to find the relevance vectors. And then use relevance vectors to find the representative vectors. The degradation model is obtained by fitting the representative vectors. Then the RUL of power MOSFETs can be estimated by extrapolating the degradation model to a failure threshold. In the prediction process, we will update the degradation model when the difference of the predictive value and measured value exceeds the predefined value. The results show that the proposed method can provide better RUL estimation accuracy for power MOSFETs.
INDIRECT ADAPTIVE INTERVAL TYPE-2 FUZZY PI SLIDING MODE CONTROL FOR A CLASS OF UNCERTAIN NONLINEAR SYSTEMS

Controller design remains an elusive and challenging problem for uncertain nonlinear dynamics. Interval type-2 fuzzy logic systems (IT2FLS) in comparison with type-1 fuzzy logic systems claim to eectively handle sys- tem uncertainties especially in the presence of disturbances and noises, but lack a formal mechanism to guarantee performance. In contrast, adaptive slid- ing mode control (ASMC) provides a robust mechanism to provide system stability against parameter changes and uncertainties, but suers from chat- tering phenomenon. In this paper, a stable indirect adaptive interval type-2 fuzzy PI sliding mode controller (AIT2FSMC) is investigated for a class of nonlinear systems in the presence of system's unmodeled dynamics and exter- nal disturbances. The added Proportional Integral (PI) structure is used to further attenuate the chattering problem that is common in sliding mode con- trol systems. The interval type-2 fuzzy adaptation law adjusts the consequent parameters of the rules based on a Lyapunov synthesis approach. Mathe- matical analysis proves the closed loop asymptotic stability, while beneting from human expert knowledge to improve transient response of the system. Application to two nonlinear systems veries the robustness of the proposed AIT2FSMC approach in the presence of uncertainties and bounded external disturbances, especially when disturbances have fast changes and large mag- nitudes.
High-Efficiency and High-Throughput On-Chip Exchange of the Continuous Phase in Droplet Microfluidic Systems

This article describes an integrated platform for the on-chip exchange of the continuous phase in droplet microfluidic systems. The drops used in this work are stabilized by amphiphilic nanoparticles. For some characterizations and applications of these nanoparticle-stabilized drops, including the measurement of adsorption dynamics of nanoparticles to the droplet surface, it is necessary to change the composition of the continuous phase from that used during the droplet generation process. Thus far, no work has reported the exchange of the continuous phase for a large number (>1 million) of drops in a microfluidic system. This article describes the design and characterization of a high-efficiency and high-throughput on-chip exchanger of the continuous phase in a continuous-flow droplet microfluidic system. The efficiency of exchange was higher than 97%. The throughput was greater than 1 million drops/min, and this can be increased further by increasing the number of parallel exchangers used. Because drops are injected into the exchanger in a continuous-flow manner, the method is directly compatible with automation to further increase its reliability and potential scale-up.
A Piecewise Response Surface Method for Simulating MEMS with Uncertain Parameters

This paper addresses the simulation and the modeling of MEMS with uncertain parameters. It focuses on an original technique derived from the piecewise perturbation method (PPM), called the piecewise response surface (PRS) method. This approach is described from a theoretical point of view. Results obtained with the PRS method and with Monte-Carlo are compared and commented in the case of a MEMS accelerometer with uncertain stiffness. The implementation of the PRS in the case of many uncertain parameters is discussed.
Acute responses of circulating microRNAs to low-volume sprint interval cycling

Low-volume high-intensity interval training is an efficient and practical method of inducing physiological responses in various tissues to develop physical fitness and may also change the expression of circulating microRNAs (miRNAs). The purpose of the present study was to examine whether miRNAs for muscle, heart, somatic tissue and metabolism were affected by 30-s intervals of intensive sprint cycling. We also examined the relationship of these miRNAs to conventional biochemical and performance indices. Eighteen healthy young males performed sprint interval cycling. Circulating miRNAs in plasma were detected using TaqMan-based quantitative PCR and normalized to Let-7d/g/i. In addition, we determined the levels of insulin-like growth factor-I, testosterone and cortisol, and anaerobic capacity. Compared to plasma levels before exercise muscle-specific miR-1 (0.12 ± 0.02 vs. 0.09 ± 0.02), miR-133a (0.46 ± 0.10 vs. 0.31 ± 0.06), and miR-133b (0.19 ± 0.02 vs. 0.10 ± 0.01) decreased (all P < 0.05), while miR-206 and miR-499 remained unchanged. The levels of metabolism related miR-122 (0.62 ± 0.07 vs. 0.34 ± 0.03) and somatic tissues related miR-16 (1.74 ± 0.27 vs. 0.94 ± 0.12) also decreased (both P < 0.05). The post-exercise IGF-1 and cortisol concentrations were significantly increased, while testosterone concentrations did not. Plasma levels of miR-133b correlated to peak power (r = 0.712, P = 0.001) and miR-122 correlated to peak power ratio (r = 0.665, P = 0.003). In conclusion sprint exercise provokes genetic changes for RNA related to specific muscle or metabolism related miRNAs suggesting that miR-133b and miR-122 may be potential useful biomarkers for actual physiological strain or anaerobic capacity. Together, our findings on the circulating miRNAs may provide new insight into the physiological responses that are being performed during exercise and delineate mechanisms by which exercise confers distinct phenotypes and improves performance.
Allied: A Framework for Executing Linked Data-Based Recommendation Algorithms

The increase in the amount of structured data published on the Web using the principles of Linked Data means that now it is more likely to find resources on the Web of Data that represent real life concepts. Discovering and recommending resources on the Web of Data related to a given resource is still an open research area. This work presents a framework to deploy and execute Linked Data based recommendation algorithms to measure their accuracy and performance in different contexts. Moreover, application developers can use this framework as the main component for recommendation in various domains. Finally, this paper describes a new recommendation algorithm that adapts its behavior dynamically based on the features of the Linked Data dataset used. The results of a user study show that the algorithm proposed in this paper has better accuracy and novelty than other state- of-the-art algorithms for Linked Data.
Secondary but not primary T cell responses are enhanced in CTLA‐4‐deficient CD8+ T cells

Negative as well as positive co‐stimulation appears to play an important role in controlling T cell activation. CTLA‐4 has been proposed to negatively regulate T cell responses. CTLA‐4‐deficient mice develop a lymphoproliferative disorder, initiated by the activation and expansion of CD4+ T cells. To assess the function of CTLA‐4 on CD8+ T cells, CTLA‐4−/‐ animals were crossed to an MHC class I‐restricted 2C TCR transgenic mouse line. We demonstrate that although the primary T cell responses were similar, the CTLA‐4‐deficient 2C TCR+ CD8+ T cells displayed a greater proliferative response upon secondary stimulation than the 2C TCR+ CD8+ T cells from CTLA‐4 wild‐type mice. These results suggest that CTLA‐4 regulates antigen‐specific memory CD8+ T cell responses.
On the homology of associative algebras

We present a new free resolution for k as an G-module, where G is an associative augmented algebra over a field k. The resolution reflects the combinatorial properties of G. Introduction. Let k be a field and let G be an associative augmented k-algebra. For many purposes one wishes to have a projective resolution of k as a G-module. The bar resolution is always easy to define, but it is often too large to use in practice. At the other extreme, minimal resolutions may exist, but they are often hard to write down in a way that is amenable to calculations. The main theorem of this paper presents a compromise resolution. Though rarely minimal, it is small enough to offer some bounds but explicit enough to facilitate calculations. As it relies heavily upon combinatorial constructions, it is best suited for analyzing otherwise tricky algebras given via generators and relations. Since several results we get as consequences of the main theorem have been obtained before through other means, this paper may be viewed as generalizing and unifying several seemingly unrelated ideas. In particular, we are generalizing Priddy's results on Koszul algebras [12], extending homology computations by Govorov [9] and Backelin [3], and complementing Bergman's methods regarding the diamond lemma [6]. Three results may be of interest. The homology of the mod p Steenrod algebra is given in terms of the homology of a new chain complex smaller than the A-algebra in Theorem 3.5. Formula (16) offers an efficient algorithm for the determination of Hilbert series, and Theorem 4.2 asserts the existence of new bounds on the torsion groups of commutative graded rings. 1. Definitions and the main theorem. Throughout this paper, k denotes any field and G is an associative k-algebra with unity. The field k embeds in G via 77: k -*G and we suppose that G has an augmentation, i.e., a k-algebra map s: G -? k for which 77 is a right inverse. S denotes a set of generators for G as a k-algebra and k(S) is the free associative k-algebra with unity on S. There is a canonical surjection f: k(S) -? G once S is chosen, and the augmentation E is determined once we know s(x) for each x E S. In particular, this means that k(S) may be augmented such that f becomes a map of augmented algebras. To S we associate a function e: S -? Z+ called a grading. In the absence of a more compelling choice we often take e to be grading by length, i.e., e(x) = 1 for Received by the editors May 23, 1983 and, in revised form, February 22, 1984. This paper was the subject of an invited one-hour address in Boulder, Colorado, during the week-long AMS summer program on Combinatorics and Algebra, June 1983. 1980 Mathematics Subject Classification (1985 Revision). Primary 16A62; Secondary 13D03, 55S10. (? )1986 American Mathematical Society 0002-9947/86 $1.00 + $. 25 per page
Effects of a Protein Preload on Gastric Emptying, Glycemia, and Gut Hormones After a Carbohydrate Meal in Diet-Controlled Type 2 Diabetes

OBJECTIVE We evaluated whether a whey preload could slow gastric emptying, stimulate incretin hormones, and attenuate postprandial glycemia in type 2 diabetes. RESEARCH DESIGN AND METHODS Eight type 2 diabetic patients ingested 350 ml beef soup 30 min before a potato meal; 55 g whey was added to either the soup (whey preload) or potato (whey in meal) or no whey was given. RESULTS Gastric emptying was slowest after the whey preload (P < 0.0005). The incremental area under the blood glucose curve was less after the whey preload and whey in meal than after no whey (P < 0.005). Plasma glucose-dependent insulinotropic polypeptide, insulin, and cholecystokinin concentrations were higher on both whey days than after no whey, whereas glucagon-like peptide 1 was greatest after the whey preload (P < 0.05). CONCLUSIONS Whey protein consumed before a carbohydrate meal can stimulate insulin and incretin hormone secretion and slow gastric emptying, leading to marked reduction in postprandial glycemia in type 2 diabetes.
Synergistic effects of substance P with insulin‐like growth factor‐1 on epithelial migration of the cornea

We find that substance P (SP) and insulin‐like growth factor‐1 (IGF‐1) demonstrate a synergistic effect on the stimulation of rabbit corneal epithelial migration in an organ culture. The addition of either SP or IGF‐1 alone did not affect epithelial migration, while the combination of SP and IGF‐1 stimulated epithelial migration in a dose‐dependent fashion. The synergistic effects of SP and IGF‐1 on corneal epithelial migration were nulled by the addition of a SP antagonist or enkephalinase. Among neurotransmitters (vasoactive intestinal peptide, calcitonin gene‐related peptide, acethylcholine chloride, norepinephrine, serotonin) or tachykinins (neurokinin A, neurokinin B, kassinin, eledoisin, physalaemin), only SP demonstrated a synergistic effect with IGF‐1 on cellular migration. In contrast, the combination of SP and IGF‐1 did not affect the incorporation of 3H‐thymidine into corneal epithelial cells. The attachment of the corneal epithelial cells to fibronectin, collagen type IV, and laminin matrices increased after treatment of the cells with SP and IGF‐1, but SP or IGF‐1 by themselves did not affect the attachment of the cells to these extracellular matrix proteins. An identical synergistic effect on corneal epithelial migration was observed when an NK‐1 receptor agonist was used in place of SP, suggesting the synergistic effect of SP and IGF‐1 might be mediated through the NK‐1 receptor system. These results suggest that the maintenance of the normal integrity of the corneal epithelium might be regulated by both humoral and neural factors. © 1996 Wiley‐Liss, Inc.
Evolution and Detection of Polymorphic and Metamorphic Malwares: A Survey

Malwares are big threat to digital world and evolving with high complexity. It can penetrate networks, steal confidential information from computers, bring down servers and can cripple infrastructures etc. To combat the threat/attacks from the malwares, anti- malwares have been developed. The existing anti-malwares are mostly based on the assumption that the malware structure does not changes appreciably. But the recent advancement in second generation malwares can create variants and hence posed a challenge to anti-malwares developers. To combat the threat/attacks from the second generation malwares with low false alarm we present our survey on malwares and its detection techniques.
Analysis and control of LTI and switched systems in digital loops via an event-based modelling

This paper is dedicated to the modelling of LTI continuous time systems in digital control loops. We consider the digital control problem on non-uniform sampling periods. Moreover, we assume that time varying delays that may have a variation range larger than a sampling period affect the closed-loop. Our goal is to present a unique model that is able to include these problems simultaneously and that can be handled by classical control synthesis tools. We present a new event based discrete-time model (an exponential uncertain system with delay) and we show that the stabilizability of this system can be achieved by finding a control for a switched polytopic system with an additive norm bounded uncertainty. The methodology is extended to the case of switched system.
Endothelial NO formation does not control myocardial O2 consumption in mouse heart.

To test whether endothelium-derived nitric oxide (NO) regulates mitochondrial respiration, NO was pharmacologically modulated in isolated mouse hearts, which were perfused at constant flow to sensitively detect small changes in myocardial O2 consumption (MVO2). Stimulation of NO formation by 10 microM bradykinin (BK) increased coronary venous nitrite release fivefold to 58 +/- 33 nM (n = 17). Vasodilatation by BK, adenosine (1 microM), or papaverine (10 microM) decreased perfusion pressure, left ventricular developed pressure (LVDP), and MVO2. In the presence of adenosine-induced vasodilatation, stimulation of endothelial NO synthesis by BK had no effect on LVDP and MVO2. Also, inhibition of NO formation by NG-monomethyl-l-arginine (l-NMMA, 100 microM) did not significantly alter LVDP and MVO2. Similarly, intracoronary infusion of authentic NO <or=2 microM did not influence LVDP or MVO2 (-1 +/- 1%). Only when NO was >2 microM were contractile dysfunction and MVO2 reduction observed. Because BK-induced stimulation of endothelial NO formation and basal NO are not sufficient to impair MVO2 in the saline-perfused mouse heart, a tonic control of the respiratory chain by endothelial NO is difficult to conceive.