Miracle-dz/UniFAR-FTUs huggingface dataset:
Functional domains in the Mig1 repressor

Mig1 is a zinc finger protein that mediates glucose repression in the yeast Saccharomyces cerevisiae. It is related to the mammalian Krox/Egr, Wilms' tumor, and Sp1 proteins and binds to a GC-rich motif that resembles the GC boxes recognized by these proteins. We have performed deletion mapping in order to identify functional domains in Mig1. We found that a small C-terminal domain comprising the last 24 amino acids mediates Mig1-dependent repression of a reporter gene. This effector domain contains several leucine-proline dipeptide repeats. We further found that inhibition of Mig1 activity in the absence of glucose is mediated by two internal elements in the Mig1 protein. A Mig1-VP16 hybrid activator was used to further investigate how Mig1 is regulated. Mig1-VP16 can activate transcription from promoters containing Mig1-binding sites and suppresses the inability of Snf1-deficient cells to grow on certain carbon sources. We found that a deletion of the SNF1 gene increases the activity of Mig1-VP16 fivefold under derepressing conditions but not in the presence of glucose. This shows that the hybrid activator is under negative control by the Snf1 protein kinase. Deletion mapping within Mig1-VP16 revealed that regulation of its activity by Snf1 is conferred by the same internal elements in the Mig1 sequence that mediate inhibition of Mig1 activity in the absence of glucose.
Hyperpolarized shifts in the voltage dependence of fast inactivation of Nav1.4 and Nav1.5 in a rat model of critical illness myopathy

Critical illness myopathy is a disorder in which skeletal muscle becomes electrically inexcitable. We previously demonstrated that a shift in the voltage dependence of fast inactivation of sodium currents contributes to inexcitability of affected fibres in an animal model of critical illness myopathy in which denervated rat skeletal muscle is treated with corticosteroids (steroid‐denervated; SD). In the current study we examined whether expression of Nav1.5 contributes to the altered voltage dependence of sodium channel inactivation in SD muscle. We used TTX and μ‐conotoxin GIIIB to selectively block Nav1.4 in SD muscle and found that the level of Nav1.5 did not correlate closely with the shift in fast inactivation. Surprisingly, we found that the voltage dependence of inactivation of Nav1.4 was similar to that of Nav1.5 in skeletal muscle in vivo. In severely affected fibres, inactivation of both Nav1.4 and Nav1.5 was shifted towards hyperpolarized potentials. We examined the role of denervation and steroid treatment in the shift of the voltage dependence of inactivation and found that both denervation and steroid treatment contribute to the shift in inactivation. Our results suggest that modulation of the voltage dependence of inactivation of both Nav1.4 and Nav1.5 in vivo contributes to loss of electrical excitability in SD muscle.
The statistical significance of nucleotide position-weight matrix matches

MOTIVATION To improve the detection of nucleotide sequence signals (e.g. promoter elements) by position-weight matrices (PWM) using the concept of statistically significant matches. RESULTS The Mksite program was originally developed for analyzing protein sequences. We report NMksite, a new version adapted to the processing of nucleotide sequences. NMksite creates PWM from nucleotide sequence block alignments or occurrence tables using three weight computation schemes. An original feature of NMksite is the numerical computation of the statistical significance of PWM matches. The utility of this concept is demonstrated in the context of the prediction of splice sites and promoter regions.
A modified particle swarm optimization rat search algorithm and its engineering application

Solar energy generation requires photovoltaic (PV) systems to be optimised, regulated, and simulated with efficiency. The performance of PV systems is greatly impacted by the fluctuation and occasionally restricted accessibility of model parameters, which makes it difficult to identify these characteristics over time. To extract the features of solar modules and build highly accurate models for PV system modelling, control, and optimisation, current-voltage data collecting is essential. To overcome these difficulties, the modified particle swarm optimization rat search algorithm is presented in this manuscript. The modified rat search algorithm is incorporated to increase the PSO algorithm’s accuracy and efficiency, which leads to better outcomes. The RSA mechanism increases both the population’s diversity and the quality of exploration. For triple diode model of both monocrystalline and polycrystalline, PSORSA has showed exceptional performance in comparison to other algorithm i.e. RMSE for monocrystalline is 3.21E-11 and for polycrystalline is 1.86E-11. Similar performance can be observed from the PSORSA for four diode model i.e. RMSE for monocrystalline is 4.14E-09 and for polycrystalline is 4.72E-09. The findings show that PSORSA outperforms the most advanced techniques in terms of output, accuracy, and dependability. As a result, PSORSA proves to be a trustworthy instrument for assessing solar cell and PV module data.
The Human Arp2/3 Complex Is Composed of Evolutionarily Conserved Subunits and Is Localized to Cellular Regions of Dynamic Actin Filament Assembly

The Arp2/3 protein complex has been implicated in the control of actin polymerization in cells. The human complex consists of seven subunits which include the actin related proteins Arp2 and Arp3, and five others referred to as p41-Arc, p34-Arc, p21-Arc, p20-Arc, and p16-Arc (Arp complex). We have determined the predicted amino acid sequence of all seven subunits. Each has homologues in diverse eukaryotes, implying that the structure and function of the complex has been conserved through evolution. Human Arp2 and Arp3 are very similar to family members from other species. p41-Arc is a new member of the Sop2 family of WD (tryptophan and aspartate) repeat–containing proteins and may be posttranslationally modified, suggesting that it may be involved in regulating the activity and/or localization of the complex. p34-Arc, p21-Arc, p20-Arc, and p16-Arc define novel protein families. We sought to evaluate the function of the Arp2/3 complex in cells by determining its intracellular distribution. Arp3, p34-Arc, and p21-Arc were localized to the lamellipodia of stationary and locomoting fibroblasts, as well to Listeria monocytogenes assembled actin tails. They were not detected in cellular bundles of actin filaments. Taken together with the ability of the Arp2/3 complex to induce actin polymerization, these observations suggest that the complex promotes actin assembly in lamellipodia and may participate in lamellipodial protrusion.
Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability.

BACKGROUND It is believed that nonadherence is the proximate cause of multidrug-resistant tuberculosis (MDR-tuberculosis) emergence. The level of nonadherence associated with emergence of MDR-tuberculosis is unknown. Performance of a randomized controlled trial in which some patients are randomized to nonadherence would be unethical; therefore, other study designs should be utilized. METHODS We performed hollow fiber studies for both bactericidal and sterilizing effect, with inoculum spiked with 0.5% rifampin- and isoniazid-resistant isogenic strains in some experiments. Standard therapy was administered daily for 28-56 days, with extents of nonadherence varying between 0% and 100%. Sizes of drug-resistant populations were compared using analysis of variance. We also explored the effect of pharmacokinetic variability on MDR-tuberculosis emergence using computer-aided clinical trial simulations of 10 000 Cape Town, South Africa, tuberculosis patients. RESULTS Therapy failure was only encountered at extents of nonadherence ≥60%. Surprisingly, isoniazid- and rifampin-resistant populations did not achieve ≥1% proportion in any experiment and did not achieve a higher proportion with nonadherence. However, clinical trial simulations demonstrated that approximately 1% of tuberculosis patients with perfect adherence would still develop MDR-tuberculosis due to pharmacokinetic variability alone. CONCLUSIONS These data, based on a preclinical model, demonstrate that nonadherence alone is not a sufficient condition for MDR-tuberculosis emergence.
A Navigating Rat Animat

This paper presents a new rat animat, a rat-sized bio-inspired robot platform currently being developed for embodied cognition and neuroscience research. The rodent animat is 150mm x 80mm x 70mm and has a differential drive, visual, proximity, and odometry sensors, x86 PC, and LCD interface. The rat animat has a bio-inspired rodent navigation and mapping system called RatSLAM which demonstrates the capabilities of the platform and framework. A case study is presented of the robot's ability to learn the spatial layout of a figure of eight laboratory environment, including its ability to close physical loops based on visual input and odometry. A firing field plot similar to rodent „non-conjunctive grid cells‟ is shown by plotting the activity of an internal network. Having a rodent animat the size of a real rat allows exploration of embodiment issues such as how the robot's sensori-motor systems and cognitive abilities interact. The initial observations concern the limitations of the design as well as its strengths. For example, the visual sensor has a narrower field of view and is located much closer to the ground than for other robots in the lab, which alters the salience of visual cues and the effectiveness of different visual filtering techniques. The small size of the robot relative to corridors and open areas impacts on the possible trajectories of the robot. These perspective and size issues affect the formation and use of the cognitive map, and hence the navigation abilities of the rat animat.
Instruction-based reuse-distance prediction for effective cache management

The effect of caching is fully determined by the program locality or the data reuse and several cache management techniques try to base their decisions on the prediction of temporal locality in programs. However, prior work reports only rough techniques which either try to predict when a cache block loses its temporal locality or try to categorize cache items as highly or poorly temporal. In this work, we quantify the temporal characteristics of the cache block at run time by predicting the cache block reuse distances (measured in intervening cache accesses), based on the access patterns of the instructions (PCs) that touch the cache blocks. We show that an instruction-based reused distance predictor is very accurate and allows approximation of optimal replacement decisions, since we can “see” the future. We experimentally evaluate our prediction scheme in various sizes L2 caches using a subset of the most memory intensive SPEC2000 benchmarks. Our proposal obtains a significant improvement in terms of IPC over traditional LRU up to 130.6% (17.2% on average) and it also outperforms the previous state of the art proposal (namely Dynamic Insertion Policy or DIP) by up to 80.7% (15.8% on average).
Dynamic characteristics of boost inverter with waveform control

The input current of single-phase inverter typically has an AC ripple component at twice the output frequency. The low-frequency current ripple can cause a reduction in both the operating lifetime of its DC source and the energy conversion efficiency of the system. In this paper1, a proposed waveform control method which can eliminate such a ripple current in boost inverter system, is discussed. The characteristics of the waveform control method in boost inverter under input voltage or wide range load variations are studied. It is validated that by including an output current feedback loop into the waveform control method, the reference voltage of the boost inverter capacitors can be instantaneously adjusted to match the new load, thereby achieving ripple mitigation for a wide load range. With the control and feedback mechanism, there is minimal level of 2ω component at the DC bus during steady state, and the transient response is rapid with negligible effect on the output voltage. Analysis, simulation and experimental results are presented to support the investigation.
Associations between Tactile Sensory Threshold and Postural Performance and Effects of Healthy Aging and Subthreshold Vibrotactile Stimulation on Postural Outcomes in a Simple Dual Task

Specific activities that require concurrent processing of postural and cognitive tasks may increase the risk for falls in older adults. We investigated whether peripheral receptor sensitivity was associated with postural performance in a dual-task and whether an intervention in form of subthreshold vibration could affect performance. Ten younger (age: 20–35 years) and ten older adults (70–85 years) performed repeated auditory-verbal 1-back tasks while standing quietly on a force platform. Foot sole vibration was randomly added during several trials. Several postural control and performance measures were assessed and statistically analyzed (significance set to α-levels of .05). There were moderate correlations between peripheral sensitivity and several postural performance and control measures (r = .45 to .59). Several postural performance measures differed significantly between older and younger adults (p < 0.05); addition of vibration did not affect outcome measures. Aging affects healthy older adults' performance in dual-tasks, and peripheral sensitivity may be a contributor to the observed differences. A vibration intervention may only be useful when there are more severe impairments of the sensorimotor system. Hence, future research regarding the efficacy of sensorimotor interventions in the form of vibrotactile stimulation should focus on older adults whose balance is significantly affected.
▼Interferon beta-1a for multiple sclerosis

In early 1996, we reviewed ▼interferon beta-1b (Betaferon - Schering Healthcare Limited), the first interferon beta to be introduced for the treatment of multiple sclerosis. The product was very expensive and the evidence for it offering real clinical advantage weak; we recommended that it should only be used as part of a clinical trial or detailed clinical audit.1 A second interferon beta, interferon beta-1a (Avonex - Biogen), has now been marketed in the UK "for the treatment of ambulatory patients with relapsing multiple sclerosis". The manufacturer claims that it "slows the progression of disability.over a 2-year period". Here, we review the evidence offered in support of this claim and assess the place of interferon beta-1a in the treatment of multiple sclerosis.
Process Structure of Semiotic Mediation in Human Development

Development of semiotic mediation of psychological functions entails construction and use of signs to regulate both interpersonal and intrapersonal psychological processes. The latter can be viewed as regulated through a hierarchy of semiotic mechanisms. It is demonstrated that semiotic mediation leads to the creation of psychological problems as well as to their solutions. Semiotic mediation guarantees both flexibility and inflexibility of the human psychological system, through the processes of abstracting generalization and contextualizing specification, which operate through the layers of the semiotic regulation hierarchy. Context specificity of psychological phenomena is an indication of general mechanisms that generate variability. Much has been written about the role of signs – semiotic mediators – in psychology over recent decades. Usually more or less elaborate claims in favor of the importance of signs – semiotic mediators, words, ‘voices’, meanings – in human psychological worlds have been made [Cole, 1996; Shweder, 1995; Wertsch, 1991, 1998]. That importance is here taken for granted, and the question addressed moves beyond the discourse about the social nature of the human individual psyche [Valsiner & Van der Veer, 2000]. In which ways could one conceptualize the functioning of signs in the regulation of psychological processes? The present elaboration is based on previous work along similar lines [Valsiner, 1996, 1997a, 1998a, 1999]. By a focus on regulation, a systemic perspective is immediately evoked. The system that is being regulated entails psychological processes of intra- and interpsychological communication. These processes are mutually related in a hierarchical organizational order – some of them (higher psychological functions, based on the operation of signs) controlling others (lower, nonintentional psychological functions, or flow of personal experience). The hierarchy can be viewed as open to changes [including reversals, or formation of intransitive order – see Valsiner, 1997d]. The person is viewed as inclusively separated from its environment [Valsiner, 1997a, 1998c]. The intrapsychological system is cultural through the inclusion of semiotic regulators into the hierarchy of psychological processes [Valsiner, 1998a]. How that system works in its immediate relatedness with the environment is the target of the present theoretical construction.
White Matter Ischemia: Time to Begin Integrating Experimental and Clinical Data

however, have these figures been estimated in a seminal study [9] . Based on anatomy data, Saver [9] estimated that in a typical human stroke the number of neurons lost each hour is 120 millions. Even more impressive and interesting for the current topic is the estimation of the damage caused to the WM. The author calculated a parallel loss of 714 km of myelinated fibers during the same time unit. It is intuitive that thrombolysis exerts its beneficial effect by reducing both the loss of neurons and the damage to WM tracts. However, although WM is found readily affected by acute ischemia in rodent models [6, 7] , the potential reversibility of this damage may offer a longer time window than that allowed for the grey matter as shown by human positron emission tomography data [10] . On the other hand, it is emerging that the biochemical mechanisms of the ischemic cascade in WM are somehow different from those in the grey matter [8] . Neuroprotective approaches should therefore also consider the WM as a possible target according to specifically developed strategies [11] . A couple of examples of existing data about neuroprotection can be revisited in this light. Recent data have pointed out a leading role for calcium in WM ischemia [8] , outlining in particular the role of intracellular calcium deposit release (so-called Trojan horse theory of calcium-mediated WM injury in acute ischemia) [12] . In in vitro experiments, blocking of calDespite the large interest of research and clinical investigators in acute stroke, for years this subject has been regarded and treated exclusively as a grey matter disease, and the focus of research has almost entirely been on neuronal compartment. This approach might have resulted in a limited understanding of the physiopathology of acute stroke and, possibly, contributed to the ensuing failure in finding neuroprotective strategies able to reduce the ischemic damage to the brain parenchyma. Only recently has the attention of some research groups been turned to the white matter (WM) [1] . The change perhaps derived from the clear appreciation of the existence of neurological conditions in which the WM is the sole or the main location of the ischemic damage; among these conditions are subcortical vascular encephalopathy and subcortical vascular dementia [2–5] . Recent laboratory developments led to the discovery that the WM is indeed vulnerable to ischemia [6, 7] and to an understanding of some of the physiopathological and biochemical mechanisms of ischemic WM damage [8] .
TDV-based Filter for Novelty and Diversity in a Real-time Pub/Sub System

Publish/Subscribe (Pub/Sub) systems have been designed to face the exponential growth of information published on the Web by subscribing to sources of interest which produce flows of items. However users may receive some information several times, or information that does not contain any new content, and conversely miss some information of interest hidden in all information received. Pub/Sub systems are consequently witnessing a real challenge to efficiently filter relevant information. We propose in this paper a scalable approach for filtering news (items) which match the user interests (expressed as subscriptions). Introducing for the first time Term Discrimination Value (TDV) in this context, which allows to measure how a term discrimines an item, we filter out in real-time items whose content has already been notified recently to the user, either in another item (filtering by novelty) or globally in his recent history (filtering by diversity). Our experiments illustrate the impact of our different parameters and confirm the scalability of our approach and the relevance of the results notified.
Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND This guideline addressed VTE prevention in hospitalized medical patients, outpatients with cancer, the chronically immobilized, long-distance travelers, and those with asymptomatic thrombophilia. METHODS This guideline follows methods described in Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines in this supplement. RESULTS For acutely ill hospitalized medical patients at increased risk of thrombosis, we recommend anticoagulant thromboprophylaxis with low-molecular-weight heparin (LMWH), low-dose unfractionated heparin (LDUH) bid, LDUH tid, or fondaparinux (Grade 1B) and suggest against extending the duration of thromboprophylaxis beyond the period of patient immobilization or acute hospital stay (Grade 2B). For acutely ill hospitalized medical patients at low risk of thrombosis, we recommend against the use of pharmacologic prophylaxis or mechanical prophylaxis (Grade 1B). For acutely ill hospitalized medical patients at increased risk of thrombosis who are bleeding or are at high risk for major bleeding, we suggest mechanical thromboprophylaxis with graduated compression stockings (GCS) (Grade 2C) or intermittent pneumatic compression (IPC) (Grade 2C). For critically ill patients, we suggest using LMWH or LDUH thromboprophylaxis (Grade 2C). For critically ill patients who are bleeding or are at high risk for major bleeding, we suggest mechanical thromboprophylaxis with GCS and/or IPC at least until the bleeding risk decreases (Grade 2C). In outpatients with cancer who have no additional risk factors for VTE we suggest against routine prophylaxis with LMWH or LDUH (Grade 2B) and recommend against the prophylactic use of vitamin K antagonists (Grade 1B). CONCLUSIONS Decisions regarding prophylaxis in nonsurgical patients should be made after consideration of risk factors for both thrombosis and bleeding, clinical context, and patients' values and preferences.