Miracle-dz/UniFAR-FTUs huggingface dataset:
Direct activation of RIP3/MLKL-dependent necrosis by herpes simplex virus 1 (HSV-1) protein ICP6 triggers host antiviral defense

Significance Receptor-interacting kinase-3 (RIP3) and its substrate mixed lineage kinase domain-like protein (MLKL) are now recognized as the core cellular regulators of programmed necrosis. Programmed necrosis is thought be involved in host defense against pathogens, but the mechanistic studies on the topic are still scarce. We discover that human herpes simplex virus 1 (HSV-1) triggers RIP3/MLKL-dependent necrosis in host cells. HSV-1 ribonucleotide reductase large subunit (ICP6) is found to be a direct activator of RIP3 and sufficient for triggering programmed necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. This study provides a clear case how host cells use programmed necrosis to mount an antiviral response. The receptor-interacting kinase-3 (RIP3) and its downstream substrate mixed lineage kinase domain-like protein (MLKL) have emerged as the key cellular components in programmed necrotic cell death. Receptors for the cytokines of tumor necrosis factor (TNF) family and Toll-like receptors (TLR) 3 and 4 are able to activate RIP3 through receptor-interacting kinase-1 and Toll/IL-1 receptor domain-containing adapter inducing IFN-β, respectively. This form of cell death has been implicated in the host-defense system. However, the molecular mechanisms that drive the activation of RIP3 by a variety of pathogens, other than the above-mentioned receptors, are largely unknown. Here, we report that human herpes simplex virus 1 (HSV-1) infection triggers RIP3-dependent necrosis. This process requires MLKL but is independent of TNF receptor, TLR3, cylindromatosis, and host RIP homotypic interaction motif-containing protein DNA-dependent activator of IFN regulatory factor. After HSV-1 infection, the viral ribonucleotide reductase large subunit (ICP6) interacts with RIP3. The formation of the ICP6–RIP3 complex requires the RHIM domains of both proteins. An HSV-1 ICP6 deletion mutant failed to cause effective necrosis of HSV-1–infected cells. Furthermore, ectopic expression of ICP6, but not RHIM mutant ICP6, directly activated RIP3/MLKL-mediated necrosis. Mice lacking RIP3 exhibited severely impaired control of HSV-1 replication and pathogenesis. Therefore, this study reveals a previously uncharacterized host antipathogen mechanism.
Microstructural change of austenite in hot working with a very high reduction.

The effects of high-reduction hot working on microstructure, deformation behavior, and mechanical properties in 18-8 stainless steel and 42 % Ni austenitic alloy have been investigated. A newly developed 150 t thermomechanical treatment simulator is used, which can provide a wide range of hot working condition. It is shown that the working temperature range in which recrystallized microstructure is obtained is broadened toward the lower side by high-reduction hot working. Recrystallized microstructure is remarkably refined by higher-reduction hot working at lower working temperature, and a very fine grain size of below 10 μm is obtained at 950°C for 18-8 stainless steel. High-reduction hot working is shown to enhance dynamic restoration due to temperature increase and accelerate static recrystallization after the working as well. The results obtained by the simulator experiments are also compared with the microstructure of the seamless pipe produced by hot extrusion, and a new thermo-mechanical
Radiographic evaluation of crestal bone levels adjacent to nonsubmerged titanium implants.

Several parameters have been described to determine success or failure in long-term evaluations of dental implants. One of these parameters is the observation of changes in peri-implant bone levels. Studies on submerged implants have analyzed the bone level changes in the pre- and post-loading phases. No such data exist for intentionally nonsubmerged implants. The purposes of this study were: (1) to test the applicability and reproducibility of a simple computer-assisted method in the evaluation of changes in peri-implant bone levels; (2) to establish a baseline for the longterm radiographic follow-up; and (3) to evaluate changes in crestal bone levels adjacent to nonsubmerged ITI implants between the 1-year and 2-year examination. Standardized periapical radiographs were obtained from 80 implants at the 1-year and 2-year follow-up examinations after their placement. The implants were located in different jaw areas of 55 patients and supported single crowns or short-span fixed partial dentures. For each implant, the distance from implant shoulder to first crestal bone contact (DIB) was measured at the proximal surfaces with a digitizer/computer assembly. Statistically significant greater mean DIB were found at the 1-year (baseline) evaluation for: (1) maxillary sites overall (4.10 x 1.02 mm (SD)) compared with mandibular sites overall (3.61 +/- 1.03 mm); (2) maxillary anterior sites (4.08 +/- 0.97 mm) compared with mandibular posterior sites (3.60 +/- 1.05 mm); and (3) maxillary posterior sites (4.13 +/- 1.12 mm) compared with mandibular posterior sites. No statistically significant changes in DIB occurred in any of the jaw locations between the 1-year and 2-year evaluations. (ABSTRACT TRUNCATED AT 250 WORDS)
Using Mandated Speed Limits to Measure the Value of a Statistical Life

In 1987 the federal government permitted states to raise the speed limit on their rural interstate roads, but not on their urban interstate roads, from 55 mph to 65 mph. Since the states that adopted the higher speed limit must have valued the travel hours they saved more than the fatalities incurred, this institutional change provides an opportunity to estimate an upper bound on the public’s willingness to trade off wealth for a change in the probability of death. Our estimates indicate that the adoption of the 65‐mph limit increased speeds by approximately 4 percent, or 2.5 mph, and fatality rates by roughly 35 percent. Together, the estimates suggest that about 125,000 hours were saved per lost life. When the time saved is valued at the average hourly wage, the estimates imply that adopting states were willing to accept risks that resulted in a savings of $1.54 million (1997 dollars) per fatality, with a sampling error roughly one‐third this value. We set out a simple model of states' decisions to adopt the 65‐mph limit that turns on whether their savings exceed their value of a statistical life. The empirical implementation of this model supports the claim that $1.54 million is an upper bound, but it provides imprecise estimates of the value of a statistical life.
DAE2FSM: Automatic generation of accurate discrete-time logical abstractions for continuous-time circuit dynamics

We abstract the I/O functionality of continuous-time dynamical systems (e.g., SPICE netlists with combinational and sequential logic) as Finite State Machines (FSMs). This enables efficient simulation of large designs implemented with less-than-perfect devices and components, and also opens the door to formal verification of transistor-level designs against higher-level specifications. In particular, our automatically generated FSMs faithfully capture the behaviour of latches, flip-flops, and circuits constructed from them. Among other technical advances, we generalize an existing (binary-only) FSM-learning approach to arbitrary I/O alphabets, which empowers it to learn high-fidelity abstractions of multi-level-discretized, multi-input/multi-output systems. Our approach, when applied to correctly functioning latches and flip-flops, is able to learn compact, multi-input FSM abstractions whose predictions closely match SPICE simulations. In addition, we have also applied our technique to produce multi-level-discretized FSM representations of digital systems that nevertheless exhibit "analogish" traits, such as an over-clocked, error-prone D-flip-flop. For such circuits, the automatically learned FSM abstraction includes additional states that characterise "failure modes" of the circuit for specific input sequences (these failure modes are also confirmed by SPICE simulations). Finally, we demonstrate that our technique is also applicable to larger and more complex multi-input, multi-output systems; for example, we are able to automatically derive an accurate FSM abstraction of a 280-transistor (BSIM4), 0-to-5 increment/decrement counter.
Metformin therapy and clinical uses

Metformin is now established as a first-line antidiabetic therapy for the management of type 2 diabetes. Its early use in treatment algorithms is supported by lack of weight gain, low risk of hypoglycaemia and its mode of action to counter insulin resistance. The drug's anti-atherosclerotic and cardioprotective effects have recently been confirmed in prospective and retrospective studies, and appear to reflect a collection of glucose-independent effects on the vascular endothelium, suppressant effects on glycation, oxidative stress and formation of adhesion molecules, stimulation of fibrinolysis and favourable effects on the lipid profile. Although avoidance of troublesome gastrointestinal tolerability issues requires careful dose titration, the risk of serious adverse events is considered low provided that contra-indications (especially with respect to renal function) are observed. As many of its actions go beyond glucose lowering, emerging evidence indicates potential benefits in other insulin-resistant states and possibly tumour suppression.
Enhancing the cellular structure and the electromechanical response of ferroelectrets - gas diffusion expansion of voided polypropylene films

Cellular electromechanically active polymers are heterogeneous materials, in which lens-shaped and usually air-filled voids are surrounded by a polymer matrix. Electrical charging leads to charge separation and trapping at the inner void surfaces and thus to macroscopic dipoles with the dimensions of the voids. The polarization can be switched by suitable electric fields. Here, a hysteresis behavior of the piezoelectric activity as well as of the dielectric displacement as functions of the poling field is observed. Therefore, in analogy to ferroelectrics, cellular electromechanically active space-charge electrets are described as ferroelectrets. Based on their heterogeneity, cellular polymers have the feature, that the dipole moments can be changed by modifying the thicknesses of the inner voids. Originally 37 /spl mu/m thick cellular (voided) polypropylene films were expanded by means of a nitrogen gas-pressure treatment, which results in a change of the film stiffness. The elastic modulus decreases from 4 MPa for not expanded films up to 1.3 MPa for the films expanded with a gas pressure of 2.0 MPa. The expansion may also lead to an increase of the transducer coefficient from 16 pC/N up to 306 pC/N. In addition to the generation of highly sensitive transducer films, gas diffusion expansion is also a suitable technique for optimizing dynamical sensor properties by adjusting the thickness-extension resonance frequency.
Adipsin and the Glucose Transporter GLUT4 Traffic to the Cell Surface via Independent Pathways in Adipocytes

Insulin increases the exocytosis of many soluble and membrane proteins in adipocytes. This may reflect a general effect of insulin on protein export from the trans Golgi network. To test this hypothesis, we have compared the trafficking of the secreted serine protease adipsin and the integral membrane proteins GLUT4 and transferrin receptors in 3T3‐L1 adipocytes. We show that adipsin is secreted from the trans Golgi network to the endosomal system, as ablation of endosomes using transferrin‐HRP conjugates strongly inhibited adipsin secretion. Phospholipase D has been implicated in export from the trans Golgi network, and we show that insulin stimulates phospholipase D activity in these cells. Inhibition of phospholipase D action with butan‐1‐ol blocked adipsin secretion and resulted in accumulation of adipsin in trans Golgi network‐derived vesicles. In contrast, butan‐1‐ol did not affect the insulin‐stimulated movement of transferrin receptors to the plasma membrane, whereas this was abrogated following endosome ablation. GLUT4 trafficking to the cell surface does not utilise this pathway, as insulin‐stimulated GLUT4 translocation is still observed after endosome ablation or inhibition of phospholipase D activity. Immunolabelling revealed that adipsin and GLUT4 are predominantly localised to distinct intracellular compartments. These data suggest that insulin stimulates the activity of the constitutive secretory pathway in adipocytes possibly by increasing the budding step at the TGN by a phospholipase D‐dependent mechanism. This may have relevance for the secretion of other soluble molecules from these cells. This is not the pathway employed to deliver GLUT4 to the plasma membrane, arguing that insulin stimulates multiple pathways to the cell surface in adipocytes.
Simulating the effects of cortical feedback in the superior colliculus with topographic maps

The superior colliculus (SC) is a neural structure found in mammalian brains that acts as a sensory hub through which visual, auditory and somatosensory inputs are integrated. This integration is used to orient the eye's fovea towards a prominent stimulus, independently of which sensory modality it was detected in. A recently observed aspect of this integration is that it is moderated by cortical feedback. As a key sensorimotor function integrating low-level sensory information moderated by the cortex, studying the SC may therefore enable us to understand how natural systems prioritize sensory computation in real-time, possibly as a result of task dependent feedback. In this paper, we focus on such a biological model. From a computational perspective, understanding this combination of bottom-up processing with top-down moderation in a model is therefore appealing. We present for the first time a behavioral model of the SC which combines the development of unisensory and multisensory representations with simulated cortical feedback. Our model demonstrates how unisensory maps can be aligned and integrated automatically into a multisensory representation. Results demonstrate that our model can capture the basic properties of the SC, and in particular they show the influence of the simulated cortical feedback on multisensory responses, reproducing the observed multisensory enhancement and suppression phenomena compared to biological studies. This suggests that our unified competitive learning approach may successfully be used to represent spatial processing that is moderated by task, and hence could be more widely applied to other, task dependent processing.
XUTools: Unix Commands for Processing Next-Generation Structured Text

Traditional Unix tools operate on sequences of characters, bytes, fields, lines, and files. However, modern practitioners often want to manipulate files in terms of a variety of language-specific constructs--C functions, Cisco IOS interface blocks, and XML elements, to name a few. These language-specific structures quite often lie beyond the regular languages upon which Unix text-processing tools can practically compute. In this paper, we propose eXtended Unix text-processing tools (xutools) and present implementations that enable practitioners to extract (xugrep), count (xuwc), and compare (xudiff) texts in terms of language-specific structures. We motivate, design, and evaluate our tools around real-world use cases from network and system administrators, security consultants, and software engineers from a variety of domains including the power grid, healthcare, and education.
Bayesian Network Anomaly Pattern Detection for Disease Outbreaks

Early disease outbreak detection systems typically monitor health care data for irregularities by comparing the distribution of recent data against a baseline distribution. Determining the baseline is difficult due to the presence of different trends in health care data, such as trends caused by the day of week and by seasonal variations in temperature and weather. Creating the baseline distribution without taking these trends into account can lead to unacceptably high false positive counts and slow detection times. This paper replaces the baseline method of (Wong et al., 2002) with a Bayesian network which produces the baseline distribution by taking the joint distribution of the data and conditioning on attributes that are responsible for the trends. We show that our algorithm, called WSARE 3.0, is able to detect outbreaks in simulated data with almost the earliest possible detection time while keeping a low false positive count. We also include the results of running WSARE 3.0 on real Emergency Department data
Steiner points in tree metrics don't (really) help

Consider an edge-weighted tree <i>T</i> = (<i>V</i>, <i>E</i>, <i>w</i> : <i>E</i> ↣ R<sup>+</sup>), in which a subset <i>R</i> of the nodes (called the <i>required</i> nodes) are colored red and the remaining nodes in <i>S</i> = <i>V</i>\<i>R</i> are colored black (and called the <i>Steiner</i> nodes). The shortest-path distance according to the edge-weights defines a metric <i>d<subscrpt>T</subscrpt></i> on the vertex set <i>V</i>. We now ask the following question: Is it possible to define another weighted tree <i>T</i>* = (<i>R</i>, <i>E</i>*, <i>w</i>* : <i>E</i>* ↣ R<sup>+</sup>), this time on <i>just the red vertices</i> so that the shortest-path metric <i>d<subscrpt>T</subscrpt></i>* induced by <i>T</i>* on the vertices in <i>R</i> is “close” to the metric <i>d<subscrpt>T</subscrpt></i> restricted to the red vertices? I.e., does there exist a weighted tree <i>T</i>* = (<i>R</i>, <i>E</i>*, <i>c</i>*) and a (small) constant α such that <i>d<subscrpt>T</subscrpt></i>(<i>u</i>, <i>v</i>) ≤ <i>d<subscrpt>T</subscrpt></i>* (<i>u</i>, <i>v</i>) ≤ α <i>d<subscrpt>T</subscrpt></i>(<i>u</i>, <i>v</i>) for any two red vertices <i>u</i>, <i>v</i> ∈ <i>R</i>? We answer this question in the affirmative, and give a linear time algorithm to obtain a tree <i>T</i>* with α ≤ 8. We also give two applications of this result: an upper bound, in which we show that emulating multicasts using unicasts can be almost as good as general multicasts for certain performance measures; and a lower bound, in which we give a simple combinatorial proof of the fact that the metric generated by a graph of girth<i>g</i> must suffer a distortion of at least &OHgr;(<i>g</i>) when approximated by a tree.
Significance of temporal and spectral acoustic cues for sexual recognition in Xenopus laevis

As in many anurans, males of the totally aquatic species, Xenopus laevis, advertise their sexual receptivity using vocalizations. Unusually for anurans, X. laevis females also advertise producing a fertility call that results in courtship duets between partners. Although all X. laevis calls consist of repetitive click trains, male and female calls exhibit sex-specific acoustic features that might convey sexual identity. We tested the significance of the carrier frequency and the temporal pattern of calls using underwater playback experiments in which modified calls were used to evoke vocal responses in males. Since males respond differently to male and female calls, the modification of a key component of sexual identity in calls should change the male's response. We found that a female-like slow call rhythm triggers more vocal activity than a male-like fast rhythm. A call containing both a female-like temporal pattern and a female-like carrier frequency elicits higher levels of courtship display than either feature alone. In contrast, a male-like temporal pattern is sufficient to trigger typical male–male encounter vocalizations regardless of spectral cues. Thus, our evidence supports a role for temporal acoustic cues in sexual identity recognition and for spectral acoustic cues in conveying female attractiveness in X. laevis.
CAHIER DU LAMSADE 271 Janvier 2008 Efficient approximation by “ low-complexity ” exponential algorithms

This paper proposes a way to bring together two seemingly “foreign” domains that are the polynomial approximation and the exact computation for NP-hard problems. We show how one can match ideas from both areas in order to design approximation algorithms achieving ratios unachievable in polynomial time (unless a very unlikely complexity conjecture is confirmed) with worst-case complexity much lower (though super-polynomial) than that of an exact computation. We then apply these ideas to two famous combinatorial optimization problems, namely, the max independent set and the min vertex cover, as well as to some other problems mainly linked to max independent set by simple approximation preserving reductions.
Interface-Based Rate Analysis of Embedded Systems

Interface-based design is now considered to be one of the keys to tackling the increasing complexity of modern embedded systems. The central idea is that different components comprising such systems can be developed independently and a system designer can connect them together only if their interfaces match, without knowing the details of their internals. We use the concept of rate interfaces for compositional (correct-by-construction) design of embedded systems whose components communicate through data streams. Using the associated rate interface algebra, two components can be connected together if the output rate of one component is "compatible" with the input rate of the other component. We formalize this notion of compatibility and show that such an algebra is non-trivial because it has to accurately model the burstiness in the arrival rates of such data streams and the variability in their processing requirements. We discuss how rate interfaces simplify compositional design and at the same time help in functional and performance verification which would be difficult to address otherwise. Finally, we illustrate these advantages through a realistic case study involving a component-based design of a multiprocessor architecture running a picture-in-picture application
A Decision-Theoretic Approach to Task Assistance for Persons with Dementia

Cognitive assistive technologies that aid people with dementia (such as Alzheimer's disease) hold the promise to provide such people with an increased level of independence. However, to realize this promise, such systems must account for the specific needs and preferences of individuals. We argue that this form of customization requires a sequential, decision-theoretic model of interaction. We describe both fully and partially observable Markov decision process (POMDP) models of a handwashing task, and show that, despite the potential computational complexity, these can be effectively solved and produce policies that are evaluated as useful by professional caregivers.