Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation of Son of sevenless by the membrane-actin linker protein ezrin

Significance Activity of the small GTPase Ras (rat sarcoma) needs to be tightly regulated because aberrant activity has a potent oncogenic effect, causing several forms of cancer as well as developmental disorders known as RASopathies. We have identified the ezrin, radixin, and moesin protein family as a previously unknown component in the control of Ras activity. Ezrin functions in the assembly of a protein complex that facilitates the encounter of Ras with its activating enzyme, Son of sevenless. Thus ezrin mediates a spatiotemporal control of Ras activity that helps coordinate and safeguard Ras signaling output. Receptor tyrosine kinases participate in several signaling pathways through small G proteins such as Ras (rat sarcoma). An important component in the activation of these G proteins is Son of sevenless (SOS), which catalyzes the nucleotide exchange on Ras. For optimal activity, a second Ras molecule acts as an allosteric activator by binding to a second Ras-binding site within SOS. This allosteric Ras-binding site is blocked by autoinhibitory domains of SOS. We have reported recently that Ras activation also requires the actin-binding proteins ezrin, radixin, and moesin. Here we report the mechanism by which ezrin modulates SOS activity and thereby Ras activation. Active ezrin enhances Ras/MAPK signaling and interacts with both SOS and Ras in vivo and in vitro. Moreover, in vitro kinetic assays with recombinant proteins show that ezrin also is important for the activity of SOS itself. Ezrin interacts with GDP-Ras and with the Dbl homology (DH)/pleckstrin homology (PH) domains of SOS, bringing GDP-Ras to the proximity of the allosteric site of SOS. These actions of ezrin are antagonized by the neurofibromatosis type 2 tumor-suppressor protein merlin. We propose an additional essential step in SOS/Ras control that is relevant for human cancer as well as all physiological processes involving Ras.
Why aren't effective teaching tools widely adopted?

Effective educational methods are available. They have been available for a long time. They are mostly behavioral, structured, fast paced, and require a high proportion of regular daily practice. Given this, it is irresponsible to invest more public funds on educational research without first installing the powerful results of the research we have already bought and paid for. The fate of highly productive educational methods in public instruction is a national shame. No highly effective educational method or program has ever been widely adopted in North America. I didn't understand and accept this until 1983, when I read the results of Project Follow Through and how they had been ignored and covered up (Carnine, 1983; Engelmann & Carnine, 1982). Here, the dear-cut results of the most extensive and most expensive educational research ever conducted were being ignored. You couldn't even get the reports out of Washington. These were the results of investing public funds, and they had run out of reports! They couldn't find them! "Call back next Monday! " To me, this was scandalous. At the time, we were getting precision teaching tried school-wide and district-wide, but had never reached the point of Follow Through's massive demonstrations of many city-wide programs, nor compared results among nine different teaching models, as Follow Through did by the end of the project. The two behavioral models (direct instruction and behavior analysis) produced the largest gains in basic skills. The self-concept oriented models actually worsened the student's achievements below the average curriculum control schools. This stopped me dead in
Machine Learning with Insufﬁcient Data Amount

—The big data era posits the basic assumption of data abundance. What should we do when we have a lot of data, but a comparable number of features or parameters to learn? In this project, we explore various supervised learning algorithms for the digit recognition task in this setting. By testing their performances with varying training data size, we draw empirical observations and discuss (unexpected) effects of having too many parameters.
Macroeconomic Implications of Variation in the Workweek of Capital

IN A TYPICAL workweek, one in every four manufacturing production workers in the United States is employed at night. This fraction fluctuates sharply over the business cycle, accounting disproportionately for business cycle changes in employment. The variation in work at night amounts to over 40 percent of the cyclical changes in the employment of manufacturing production workers. While cyclical movements in shiftwork are pervasive in many manufacturing industries, there are also some nonmanufacturing industries in which such variation is important. Changes in the number, as well as the length, of shifts affect the workweek of capital. Demonstrating the importance of the workweek of capital for studying business cycles is the main goal of this paper. In most business cycle models, the capital stock is taken as quasi-fixed. Cyclical variation in output arises from applying more or less labor to a fixed capital stock. This property of capital should lead to diminishing marginal product of labor, to countercyclical real wage and average product of labor, and potentially to capacity constraints. Keynesian students of cyclical productivity, however, have long realized the importance of variable utilization of capacity. Their models, which admit the persistent unemployment or underemployment of both capital and labor, can readily dispense with the implications of diminishing marginal product of labor. Work on equilibrium business cycles also finds
‘On of the Princypalle Havenes of the See’: The Port of Famagusta and the Ship Graffiti in the Church of St George of the Greeks, Cyprus

In its 1000‐year history the port has been the source of triumph and tragedy for the city of Famagusta, being the conduit through which flowed both enormous wealth and destruction. Today the French medieval and Greek Orthodox churches, and the Venetian walls, though ruined, still carry physical traces of this turbulent society in the form of ship graffiti. Though such images are often classified as ‘low‐art’, they are nevertheless imbued with a deep social significance, which the maritime historian can yet use to get a glimpse of an important, though virtually‐forgotten, heritage in the Eastern Mediterranean. © 2007 The Author
Stability analysis of multi-agent system with leaders and time delays under Gaussian profiles

In this paper we consider stability analysis of a class of of Multi-agent system with leaders and time delays under Gaussian profiles. The leaders and the followers are included in the proposed system, and only the leaders have the knowledge about the environment. The emergent behavior of the system motion is the result of a balance between inter-individuals interactions and the simultaneous interactions of the system with their environment. The paper considers some condition under which it shows that for Gaussian attractant/repellent profiles the leaders and followers with time delays will aggregate and form a cohesive cluster of finite size in a finite time under some mild assumptions.
Wheeler and Fano Impedance Matching [Antenna designer's notebook]

A recent series of articles in this Magazine's Antenna Designer's Notebook column highlighted Fano's fundamental work on the limitations of the impedance matching of arbitrary impedances and its application to antenna design. Lopez, using Harold Wheeler's methodology, constructed a closed-form solution to the nonlinear simultaneous equations of Fano. This article presents the Wheeler methodology that was the basis for this work, and is still invaluable in the understanding of optimum impedance matching.
Grooved Upper Grinding Stones of Saddle Querns in Israel

Abstract Grooved upper grinding stones of saddle mills are rare in the southern Levant. The grooves are either hand-grips or are meant to hold a rod used to move the stone back and forth. Two stones with grooves from Tel Tannim are very similar to one from Tell Qasile dated to the Iron Age and to those from Tell Halaf in Mesopotamia where they are the main type, suggesting that this type originated in the north. An unusual stone from Horvat 'Ein Koveshim is identical to one from Sarepta in southern Lebanon, suggesting that these are of a Phoenician type.
Temperature Dependence of Water Vibrational Spectrum: A Molecular Dynamics Simulation Study

Vibrational spectroscopy studies show that the bulk water bending band becomes narrower with increasing temperature (Marechal, Y. J. Mol. Struct. 1994, 322, 105). Since this counterintuitive effect is not associated with the quantum nature of nuclear motion a molecular dynamics (MD) simulation is expected to reproduce it even in the classical limit. We have performed a classical MD simulation of the flexible simple point charge (SPC) and extended SPC (SPC/E) water models to determine the temperature dependence of the bulk water vibrational spectrum. The intramolecular water potential proposed by Toukan and Rahman, including a stretch−bend coupling term, was applied. We performed MD simulations at −4 and 80 °C to compare the calculated vibrational spectra, in particular, the band associated with the bending mode, with the experiment. The experimentally determined narrowing of the bending band with increasing temperature is not reproducible by MD simulation with the applied force field. However, the results.
Accumulation of Minor Alleles of Common SNPs in Schizophrenia

Schizophrenia is a common neuropsychiatric disorder with a lifetime risk of 1%. A number of large scale genome wide association studies have identified numerous individual risk single nucleotide polymorphisms (SNPs) whose precise roles in schizophrenia remain unknown. Accumulation of many of these risk alleles has been found to be a more important risk factor. Consistently, recent studies showed a role for enrichment of minor alleles (MAs) in complex diseases. Here we studied the role of MAs in general in schizophrenia using public datasets. Relative to matched controls, schizophrenia cases showed higher minor allele content (MAC), especially for the sporadic cases. By linkage analysis, we identified 82 419 SNPs that could be used to predict 2.2% schizophrenia cases with 100% certainty. Pathway enrichment analysis of these SNPs identified 17 pathways, 15 of which are known to be linked with Schizophrenia with the remaining 2 associated with other mental disorders. These results suggest a role for a collective effect of MAs in schizophrenia and provide a method to genetically screen for schizophrenia. Abbreviations MAs minor alleles MAC minor allele content MAF minor allele frequency AUC under the curve TPR True positive rate
An efficient framework for parallel and continuous frequent item monitoring

In high‐speed network monitoring, the ever‐growing traffic calls for a high‐performance solution for the computation of frequent items. The increasing number of cores in the current commodity multi‐core processors opens up new opportunities in parallelization. In this paper, we present a novel precision integrated framework (PRIF) that exploits the great parallel capability of multi‐cores to speed up the famous frequent algorithm. PRIF equally distributes the input data stream into sub‐threads that use the optimized weighted frequent algorithm to track local frequent items. The items with frequency increments exceeding a pre‐defined threshold are sent to a merging thread which is able to return the global continuous ε‐deficient frequent items. The theoretical correctness and complexity analyses are presented. Experiments with real and synthetic traces confirm the theoretical analyses and demonstrate the excellent performance as well as the effects of parameters and data skewness. The results show that PRIF is able to provide continuous frequent items and near‐linear speedup at the cost of greater memory use. Copyright © 2013 John Wiley & Sons, Ltd.
The GTPase Activity of Murine Guanylate-binding Protein 2 (mGBP2) Controls the Intracellular Localization and Recruitment to the Parasitophorous Vacuole of Toxoplasma gondii*

Background: Elucidation of the biochemical and biological function of IFN-γ induced mGBP2. Results: Mutations in the G-domain of mGBP2 inhibit GTPase activity and multimerization resulting in failure in the recruitment to T. gondii. Conclusion: The GTPase activity is essential for physiological intracellular localization and intersection of T. gondii. Significance: This study identifies residues relevant for GTP hydrolysis and essential for biological function of mGBP2 in host-pathogen interaction. One of the most abundantly IFN-γ-induced protein families in different cell types is the 65-kDa guanylate-binding protein family that is recruited to the parasitophorous vacuole of the intracellular parasite Toxoplasma gondii. Here, we elucidate the relationship between biochemistry and cellular host defense functions of mGBP2 in response to Toxoplasma gondii. The wild type protein exhibits low affinities to guanine nucleotides, self-assembles upon GTP binding, forming tetramers in the activated state, and stimulates the GTPase activity in a cooperative manner. The products of the two consecutive hydrolysis reactions are both GDP and GMP. The biochemical characterization of point mutants in the GTP-binding motifs of mGBP2 revealed amino acid residues that decrease the GTPase activity by orders of magnitude and strongly impair nucleotide binding and multimerization ability. Live cell imaging employing multiparameter fluorescence image spectroscopy (MFIS) using a Homo-FRET assay shows that the inducible multimerization of mGBP2 is dependent on a functional GTPase domain. The consistent results indicate that GTP binding, self-assembly, and stimulated hydrolysis activity are required for physiological localization of the protein in infected and uninfected cells. Ultimately, we show that the GTPase domain regulates efficient recruitment to T. gondii in response to IFN-γ.
Whole-body (18)F-FDG PET identifies high-risk myeloma.

UNLABELLED The purpose of this study was to evaluate the clinical utility of whole-body PET with (18)F-FDG in patients with multiple myeloma and related monoclonal diseases. METHODS Between July 1, 1996, and July 2000, 98 (18)F-FDG PET scans were obtained for 66 patients, with 25 patients having 2 or more scans. The results were compared with routine clinical and staging information, including CT and MRI scans, as indicated. Of the 66 patients, 16 had previously untreated active myeloma, 14 had monoclonal gammopathy of undetermined significance (MGUS), 10 had disease in remission, and 26 had relapsing disease. RESULTS Negative whole-body (18)F-FDG PET findings reliably predicted stable MGUS. Of the 14 MGUS patients with follow-up of 3-43+ mo, myeloma has developed in only 1 (7%), at 8 mo. Conversely, the 16 previously untreated patients with active myeloma all had focal or diffusely positive scan findings. Four (25%) of 16 previously untreated patients with positive (18)F-FDG PET findings had negative full radiologic surveys. Another 4 (25%) of 16 patients had focal extramedullary disease. This was confirmed by biopsy or other imaging techniques. Extramedullary uptake also occurred in 6 (23%) of 26 patients with relapse. This extramedullary uptake was a very poor prognostic factor both before treatment and at relapse. For example, median survival was 7 mo for patients with disease relapse. Persistent positive (18)F-FDG PET findings after induction therapy predicted early relapse. In 13 (81%) of 16 patients with relapsing disease, new sites of disease were identified. The (18)F-FDG PET results were especially helpful in identifying focal recurrent disease in patients with nonsecretory or hyposecretory disease amenable to local irradiation therapy, which was used in 6 patients. CONCLUSION Whole-body (18)F-FDG PET provides important prognostic information, which is clinically useful and complementary to conventional methods of evaluating plasma cell disorders. (18)F-FDG PET is a unique tool for evaluation of nonsecretory myeloma. Residual or recurrent disease after therapy, especially extramedullary disease, is a poor prognostic factor.
The Influence of Adaptive Multicoding on Mutual Information and Channel Capacity for Uncertain Wideband CDMA Rayleigh Fading Channels

We consider the problem of adaptive modulation for wideband DS-CDMA Rayleigh fading channels with imperfect channel state information (CSI). We assume a multidimensional signal subspace spanned by a collection of random spreading codes (multicoding) and study the effects of both the subspace dimension and the probability distribution of the transmitted symbols on the mutual information between the channel input and output in the presence of uncertainty regarding the true state of the channel. We develop approximations for the mutual information as well as both upper and lower bounds on the mutual information that are stated explicitly in terms of the dimension of the signal constellation, the number of resolvable fading paths on the channel, the current estimate of channel state, and the mean-squared-error of the channel estimate. We analyze these approximations and bounds in order to quantify the impact of signal dimension and symbol distribution on system performance.
Plasma Factors During Chronic HIV-1 Infection Impair IL-12 Secretion by Myeloid Dendritic Cells via a Virus-Independent Pathway

Objective:Myeloid dendritic cell (mDC) dysfunction during HIV infection may hinder the formation of both innate and adaptive immune responses and contribute to pathogenesis. Our objective was to determine whether circulating factors during chronic HIV infection impair mDC function with respect to secretion of IL-12, a pro-Th1 cytokine, and T-cell stimulatory capacity. Particular focus was placed on the effect of combination antiretroviral therapy (cART) and the role of HIV itself on mDC function. Methods:Monocyte-derived DC (moDC) from uninfected donors were exposed to plasma from HIV-infected individuals before Toll-like receptor (TLR) stimulation. Cytokine secretion was measured via cytokine bead arrays, and T-cell proliferation and IFN&ggr; secretion was evaluated after coculture with naive CD4+ T cells. Expression of genes central to TLR-mediated signal transduction was analyzed via quantitative reverse transcriptase—polymerase chain reaction (qRT-PCR) arrays and western blot. Results:Exposure of monocyte-derived DC to plasma from untreated HIV-infected donors suppressed secretion of IL-12, and impaired Th1-skewing of CD4+ T cells. The suppressive effect was less by plasma donors receiving cART. Removal of virus from plasma did not relieve suppression nor was IL-12 secretion decreased on addition of HIV to control plasma. On a transcriptional level, decreased expression of IKK&bgr;, a key regulator in the TLR/NF-kappaB signaling pathway, corresponded to suppressed cytokine secretion. Conclusions:Plasma factors during chronic HIV infection impair mDC function in a manner that likely impacts the formation of immune responses to HIV, opportunistic pathogens, and vaccines. Despite partial alleviation by cART, this suppression was not directly mediated by HIV.
Ca2+ Binding/Permeation via Calcium Channel, CaV1.1, Regulates the Intracellular Distribution of the Fatty Acid Transport Protein, CD36, and Fatty Acid Metabolism*

Background: Ca2+ binding and/or permeation via CaV1.1 in skeletal muscle activates CaMKII. Results: Mice with a Ca2+ binding/permeation defect in CaV1.1 have increased body fat, reduced fatty acid metabolism, and altered CD36 distribution. Conclusion: CaV1.1 regulates CD36 distribution and fatty acid metabolism. Significance: New therapeutic targets are identified to increase skeletal muscle energy expenditure. Ca2+ permeation and/or binding to the skeletal muscle L-type Ca2+ channel (CaV1.1) facilitates activation of Ca2+/calmodulin kinase type II (CaMKII) and Ca2+ store refilling to reduce muscle fatigue and atrophy (Lee, C. S., Dagnino-Acosta, A., Yarotskyy, V., Hanna, A., Lyfenko, A., Knoblauch, M., Georgiou, D. K., Poché, R. A., Swank, M. W., Long, C., Ismailov, I. I., Lanner, J., Tran, T., Dong, K., Rodney, G. G., Dickinson, M. E., Beeton, C., Zhang, P., Dirksen, R. T., and Hamilton, S. L. (2015) Skelet. Muscle 5, 4). Mice with a mutation (E1014K) in the Cacna1s (α1 subunit of CaV1.1) gene that abolishes Ca2+ binding within the CaV1.1 pore gain more body weight and fat on a chow diet than control mice, without changes in food intake or activity, suggesting that CaV1.1-mediated CaMKII activation impacts muscle energy expenditure. We delineate a pathway (Cav1.1→ CaMKII→ NOS) in normal skeletal muscle that regulates the intracellular distribution of the fatty acid transport protein, CD36, altering fatty acid metabolism. The consequences of blocking this pathway are decreased mitochondrial β-oxidation and decreased energy expenditure. This study delineates a previously uncharacterized CaV1.1-mediated pathway that regulates energy utilization in skeletal muscle.
Power and Location Optimization for Full-Duplex Decode-and-Forward Relaying

Full-duplex transmission is a promising technique to enhance the capacity of relay communications. In this paper, we investigate the power and location optimization for full-duplex decode-and-forward (DF) relaying systems. The outage probability is adopted as the optimization criterion and a two-dimensional (2D) optimization problem is formulated for systems with and without the direct source-destination link. Analytical and numerical results are provided to demonstrate advantages of the power and location optimization. More interestingly, the effect of residual self-interference (RSI) introduced by full-duplex transmission is investigated in terms of the optimal power allocation and relay location deployment and the outage probability performance improvement. Furthermore, we show that the minimal outage probability can be achieved via joint power-location optimization. The effect of power optimization on the outage performance is also compared between full-duplex and half-duplex relaying.
Flatness principle extension to linear fractional MIMO systems: Thermal application

This paper concerns the application of flatness principle to fractional MIMO systems in the pseudo-state-space representation. The aim here is to compute linear flat outputs for linear controllable time-invariant systems in polynomial matrix form. The defining matrices expressed with the system variables in terms of a linear flat output and its derivatives define the kernel of a polynomial matrix. Flatness in path planning is used to determine the controls to apply without integrating any differential equations when the trajectory is fixed. Several developments have been made for LTI systems, however concerning fractional differentiation systems, especially in MIMO, developments are still to be made. The aim of this paper is to apply flatness principle using polynomial matrices for linear fractional MIMO systems.
De Gustibus Non Est Disputandum

Dans la microeconomie standard, les preferences du consommateur sont considerees comme des donnees (variable exogene). George Stigler et Gary Becker cherchent ici a endogeneiser ces preferences, ce qui les place alors sur un des terrains favoris des sociologues : l’analyse des gouts. Notre collegue Christophe Longuet nous offre une traduction inedite de cet article canonique precedee d’une presentation. Son travail, en tout point remarquable, vous sera certainement tres utile.