Miracle-dz/UniFAR-FTUs huggingface dataset:
BMC Systems Biology

Background: Mathematical modeling of real-life processes often requires the estimation of unknown parameters. Once the parameters are found by means of optimization, it is important to assess the quality of the parameter estimates, especially if parameter values are used to draw biological conclusions from the model. Results: In this paper we describe how the quality of parameter estimates can be analyzed. We apply our methodology to assess parameter determinability for gene circuit models of the gap gene network in early Drosophila embryos. Conclusion: Our analysis shows that none of the parameters of the considered model can be determined individually with reasonable accuracy due to correlations between parameters. Therefore, the model cannot be used as a tool to infer quantitative regulatory weights. On the other hand, our results show that it is still possible to draw reliable qualitative conclusions on the regulatory topology of the gene network. Moreover, it improves previous analyses of the same model by allowing us to identify those interactions for which qualitative conclusions are reliable, and those for which they are ambiguous.
Conductance histogram evolution of an EC–MCBJ fabricated Au atomic point contact

This work presents a study of Au conductance quantization based on a combined electrochemical deposition and mechanically controllable break junction (MCBJ) method. We describe the microfabrication process and discuss improved features of our microchip structure compared to the previous one. The improved structure prolongs the available life of the microchip and also increases the success rate of the MCBJ experiment. Stepwise changes in the current were observed at the last stage of atomic point contact breakdown and conductance histograms were constructed. The evolution of 1G0 peak height in conductance histograms was used to investigate the probability of formation of an atomic point contact. It has been shown that the success rate in forming an atomic point contact can be improved by decreasing the stretching speed and the degree that the two electrodes are brought into contact. The repeated breakdown and formation over thousands of cycles led to a distinctive increase of 1G0 peak height in the conductance histograms, and this increased probability of forming a single atomic point contact is discussed.
Diversity-Multiplexing Tradeoff of Symmetric MIMO Interference Channels with Partial CSIT

In this paper, we propose a transmission scheme for the two-user symmetric multiple antenna interference channel (IFC) and show that the proposed transmission scheme can achieve the optimal diversity-multiplexing tradeoff (DMT) of the channel. The proposed transmission scheme requires only limited channel state information at the transmitter (CSIT) and is suitable for practical implementation. The limited CSIT is obtained by letting the destinations quantize the required information and feed back to the sources. Rules for implementing the quantization are proposed and the number of bits needed to represent the quantization is calculated. It is shown that for the proposed transmission scheme to be DMT optimal, the number of feedback bits should increase in log scale with respect to signal-to-noise ratio.
Exploiting Common Sparsity for Frequency-Domain Wideband Channel Estimation at mmWave

Hybrid architectures reduce power consumption for MIMO systems at millimeter wave (mmWave) with respect to all-digital solutions. Fast configuration of hybrid arrays is one of the main challenges to be solved to unlock the potential of mmWave in high mobility scenarios. Channel estimation is one of the means of obtaining the information needed to configure these arrays. Prior work on channel estimation at mmWave considers a frequency-flat narrowband channel model, although the the mmWave channel is intrinsically wideband and frequency-selective. In this paper, we design a frequency-domain algorithm that leverages the sparsity in the channel to estimate the frequency-selective mmWave channel. We evaluate this technique by simulation and study its complexity, comparing the trade-offs complexity-overhead-performance to those of previous approaches. We conclude that the proposed approach outperforms previous algorithms, providing a better performance at a lower computational cost.
Immobilization of Neutral Protease from Bacillus subtilis for Regioselective Hydrolysis of Acetylated Nucleosides: Application to Capecitabine Synthesis

This paper describes the immobilization of the neutral protease from Bacillus subtilis and its application in the regioselective hydrolysis of acetylated nucleosides, including building blocks useful for the preparation of anticancer products. Regarding the immobilization study, different results have been obtained depending on the immobilization procedure. Epoxy hydrophobic carriers gave a poorly stable derivative that released almost 50% of the immobilized protein under the required reaction conditions. On the contrary, covalent immobilization on a differently activated hydrophilic carrier (agarose) resulted in very stable enzyme derivatives. In an attempt to explain the obtained enzyme immobilization results, the hypothetical localization of lysines on the enzyme surface was predicted in a 3D structure model of B. subtilis protease N built in silico by using the structure of Staphylococcus aureus metalloproteinase as the template. The immobilized enzyme shown a high regioselectivity in the hydrolysis of different peracetylated nucleosides. A stable enzyme derivative was obtained and successfully used in the development of efficient preparative bioprocesses for the hydrolysis of acetylated nucleosides, giving new intermediates for the synthesis of capecitabine in high yield.
Spatial-temporal nonparametric background subtraction in dynamic scenes

Traditional background subtraction methods model only temporal variation of each pixel. However, there is also spatial variation in real word due to dynamic background such as waving trees, spouting fountain and camera jitters, which causes the significant performance degradation of traditional methods. In this paper, a novel spatial-temporal nonparametric background subtraction approach (STNBS) is proposed to effectively handle dynamic background by modeling the spatial and temporal variations simultaneously. Specially, for each pixel in an image, we adaptively maintain a sample consisting of pixels observed in previous frames. At current frame, for a particular pixel, the proposed method estimates the probabilities of observing this pixel based on samples of its neighboring pixels. The pixel is labeled as background if one of these estimated probabilities is larger than a fixed threshold. All samples are adaptively updated over time. Experimental results on several challenging sequences show that the proposed method achieves the best performance than two state-of-the-art algorithms.
Evidence for mediated protein uptake by amphibian oocyte nuclei

The objective of this investigation was to determine whether there is mediated transport of endogenous proteins across the nuclear envelope. For this purpose, we studied the nuclear uptake of a 148,000-dalton Rana oocyte polypeptide (RN1) and compared its actual uptake rate with the rate that would be expected if RN1 crossed the envelope by simple diffusion through the nuclear pores. Nuclear uptake was studied in two ways: first, oocytes were incubated in L-[3H]leucine for 1 h and, at various intervals after labeling, the amount of 3H-RN1 present in the nucleoplasm was determined. Second, L-[3H]leucine-labeled nuclear extracts, containing RN1, were microinjected into the cytoplasm of nonlabeled cells, and the proportion of 3H-RN1 that subsequently entered the nucleus was measured. It was found that RN1 can readily penetrate the nuclear envelope; for example, after 6 h, approximately 36% of the newly synthesized RN1 and 17% of the injected RN1 had entered the nucleus. The diffusion rate through pores having a radius of 45 A was calculated for several possible molecular configurations of RN1. Using axial ratios of 34, 7.5, 2, and 1, the estimated times required to reach 63% of diffusion equilibrium are 757, 468, 6,940 h, and infinity, respectively. Even assuming an axial ratio of 7.5 (the most diffusive configuration) and an equilibrium distribution of 45, simple diffusion through the pores could account for only approximately 1/20 the observed nuclear uptake of RN1. This and other comparisons indicate that some form of mediated transport is involved in the nucleocytoplasmic exchange of this polypeptide.
Intra-individual stability over time of standardized anti-Mullerian hormone in FMR1 premutation carriers.

BACKGROUND Carriers of a premutation (CGG repeat length 55-200) in the fragile X mental retardation (FMR1) gene are at risk for primary ovarian insufficiency (FXPOI). The anti-Müllerian hormone (AMH) level acts as a useful marker of ovarian follicle reserve and, thus, may serve to predict when this ovarian reserve becomes too low to sustain ovarian function. We investigated the intra-individual variation of AMH levels over time for premutation carriers compared with non-carriers. METHODS We determined AMH levels in blood samples from 240 women ascertained through fragile X families, of which 127 were premutation carriers and 113 were non-carriers. Linear mixed models were used to assess the effect of age and premutation status on AMH levels and to determine a modeled AMH value. The stability over time of the deviation of observed AMH levels from modeled levels, referred to as standardized AMH values, was assessed through correlation coefficients of 41 longitudinal samples. RESULTS At all ages, premutation carriers exhibited lower AMH levels. For all women, AMH was found to decrease by 10% per year. The added effect of having a premutation decreased AMH levels by 54%. The deviation of an individual's AMH level from the modeled value showed a reasonable intra-individual correlation. The Pearson correlation coefficient of two samples taken at different ages was 0.36 (P = 0.05) for non-carriers and 0.69 (P = 0.01) for carriers. CONCLUSIONS We developed a unique standardized AMH value, taking FMR1 premutation status and the subject's age into account, which appears to be stable over time and may serve as a predictor for FXPOI after further longitudinal assessment.
Autonomy and religious education: lessons from a six-year evaluation of an educational reform in an Israeli school network

This study investigated the tension that exists between promoting an educational agenda and practising an educational approach which emphasises autonomy within the framework of religious education. Our main thesis is that every educational deed contains a dialectical tension between endorsing an educational agenda and the promotion of autonomy. Moreover, this tension is not restricted to religious education. The intensity of such a conflict varies in accordance with the flexibility (or inflexibility) of the dogma, the conceptual cohesion of the educational agenda and the perceived importance of granting autonomy to students. The more cohesive and inflexible the educational agenda is, the greater the danger that autonomy will be discarded. The present research examined an educational reform implemented in the National-Religious School Network in Israel, which included the promotion of autonomy among principals, teachers and students. Conducted over a six-year period (2006–2012), the research employed both qualitative and quantitative methodologies and involved various stakeholders in the school network. The multifaceted picture that emerged of the relationship between educational autonomy and religious agenda is presented.
Fingerprinting-based localization using accelerometer information in wireless sensor networks

This paper considers the localization problem of sensors in mobile wireless sensor networks. It proposes a combined localization technique, using both fingerprinting and accelerometer information. The proposed approach consists of two phases. In the first one, a power map is constructed over the surveillance area. In the second phase, nodes are localized and a first position estimate is computed using the constructed power map. A second estimate is also given using accelerometer information. Both estimates are then combined using interval analysis, solutions being boxes including the real positions of the nodes. Simulation results show that the combined method improves the positioning performance, compared to methods based only on fingerprinting or accelerometer information.
RETROSPECTIVE: Single-ISA Heterogeneous Multi-Core Architectures for Multithreaded Workload Performance

This work began in 2001 when multicore processors had just started appearing. It was apparent to all a major technological shift was happening. Technological shifts typically represent tremendous opportunities to rethink the assumptions that shaped past products. In our case (during a fruitful collaboration over a number of years) we chose to question two assumptions, (1) that all cores should be identical, and (2) that they should be distinct and separable with no shared functional blocks. The work we are discussing here is the result of questioning that first assumption. The earliest multicores were not aggressive – two cores stamped onto the same die with no communication or common logic between them. They soon became more truly multicore, with communication between them, peripheral logic (and eventually caches) shared, etc. But even in the early 2000’s, all roadmaps were clearly symmetric multiprocessing. So why was this technological shift the right time to question the "all cores identical" assumption? In a multiprocessor composed of uniprocessor chips, particularly if you optimized the cores to coexist in a heterogeneous design, it would require two (or more) distinct fab runs to produce those chips, and all the fixed costs associated with the production of each chip. For a single-chip heterogeneous multicore, you could introduce all the heterogeneity you wanted, and still require only a single fab run to produce it. The economies of scale no longer favored homogeneity. At that time, the primary mechanism being deployed (or even discussed in the literature) to save power for applications that did not utilize the whole processor was clock gating. If a 4-wide superscalar was getting an IPC of 0.5, we could clock gate most of the ALUs and some other structures. But the gains were limited to a small percentage of total power. Besides, this was a time when power was already a first class concern, voltage scaling had more or less stopped, and static power (which clock gating could not target) was already significant. It was clear that we needed a dramatically better power reduction technique.
Is there a role for genetic testing in patients with melanoma?

Autosomal dominant inheritance of mutations in the INK4a/ARF locus or the CDK4 gene may confer a high risk of cutaneous melanoma development. The penetrance of INK4a/ARF mutations is influenced by UV exposure. Inherited variants in the melanocortin-1 receptor also confer increased risk of cutaneous melanoma. Features associated with increased genetic susceptibility to cutaneous melanoma include the presence of multiple affected first-degree relatives on one side of the family, multiple primary melanomas in the same individual, earlier age of onset, and the presence of multiple atypical nevi, but none of these factors reliably predicts for the presence of INK4a/ARF mutations. It is currently premature to offer predictive DNA testing for melanoma outside of defined research protocols. This is because of (1) the low likelihood of finding mutations in known melanoma susceptibility genes, even in more than 60% of melanoma-prone kindreds; (2) the broad confidence limits on current estimates of lifetime penetrance of INK4a/ARF mutations and the wide variation in this penetrance with locality; (3) a high “background” incidence of melanoma in non-mutation carriers in melanoma-prone families; (4) current uncertainties about the factors determining the functionality and phenotypic expression of the trait among carriers of these mutations (penetrance), even if found; and (5) the lack of proved efficacy of melanoma prevention and surveillance strategies, even for mutation carriers. Rather than singling out those deemed to be at high risk because of family history, all patients carrying risk factors for cutaneous melanoma should be subject to stringent programs of sun protection and skin surveillance.
Structure of Monomeric Yeast and Mammalian Sec61 Complexes Interacting with the Translating Ribosome

Nascent Chains Revealed Detailed analysis of protein translation and translocation across membranes requires the identification and structural analysis of intermediates involved in these processes (see the Perspective by Kampmann and Blobel). Seidelt et al. (p. 1412, published online 29 October) report the visualization by cryo-electron microscopy of a nascent polypeptide chain in the tunnel of the ribosome at 5.8 angstroms. This resolution allows analysis of the conformation and distinct contacts of the nascent chain within the ribosomal tunnel, which suggests a mechanism by which translational stalling is induced by this peptide. Protein translocation across cellular membranes involves the Sec61 protein, a component of a protein-conducting channel. Whether Sec61 acts as a monomer or as an oligomer during protein translocation has been unclear. Becker et al. (p. 1369, published online 29 October) describe active yeast and mammalian ribosome-Sec61 structures that show the Sec61 complex interacting with the ribosome and a nascent secretory protein signal sequence. The analysis unambiguously reveals that the active protein-conducting channel is a single Sec61 copy with its central pore serving as conduit for the nascent polypeptide. A single copy of a protein-conducting channel molecule provides a conduit for polypeptide translocation across membranes. The trimeric Sec61/SecY complex is a protein-conducting channel (PCC) for secretory and membrane proteins. Although Sec complexes can form oligomers, it has been suggested that a single copy may serve as an active PCC. We determined subnanometer-resolution cryo–electron microscopy structures of eukaryotic ribosome-Sec61 complexes. In combination with biochemical data, we found that in both idle and active states, the Sec complex is not oligomeric and interacts mainly via two cytoplasmic loops with the universal ribosomal adaptor site. In the active state, the ribosomal tunnel and a central pore of the monomeric PCC were occupied by the nascent chain, contacting loop 6 of the Sec complex. This provides a structural basis for the activity of a solitary Sec complex in cotranslational protein translocation.
Head pose estimation through multi-class face segmentation

The aim of this work is to explore the usefulness of face semantic segmentation for head pose estimation. We implement a multi-class face segmentation algorithm and we train a model for each considered pose. Given a new test image, the probabilities associated to face parts by the different models are used as the only information for estimating the head orientation. A simple algorithm is proposed to exploit such probabilites in order to predict the pose. The proposed scheme achieves competitive results when compared to most recent methods, according to mean absolute error and accuracy metrics. Moreover, we release and make publicly available a face segmentation dataset1 consisting of 294 images belonging to 13 different poses, manually labeled into six semantic regions, which we used to train the segmentation models.
Consensus Disturbance Rejection With Disturbance Observers

This paper deals with consensus disturbance rejection of network-connected dynamic systems using disturbance observers. The control objective of consensus disturbance rejection is to achieve a common state trajectory for the network-connected subsystems that are under deterministic disturbances. The difference from the existing disturbance rejection methods is that only the relative state information is used for disturbance rejection, and as a consequence of using the relative state information, only the part of the disturbances that affect the common trajectories will be rejected. The conditions for designing disturbance observers for consensus control are identified for networked-connected multiagent systems. Certain features of the individual subsystems are analyzed for possible implementation of disturbance-observer-based rejection, and the disturbance observers are designed based on the relative state information obtained from the neighboring subsystems under different network connections. When the network connectivity is available for the disturbance observer design, consensus disturbance rejection is achieved for a directed network with a spanning tree. A fully distributed consensus disturbance rejection design is presented for an undirected network with the use of adaptive parameters for the estimation of the unknown network connectivity. Disturbance observers are also proposed for disturbance rejection in the leader-follower consensus control.
Determinants of the Cost-Effectiveness of Statins

OBJECTIVES: To examine the cost-effectiveness of statins in relation to different measures of effectiveness, differences in efficacy among individual statins, and the risk of coronary heart disease. Efficacy is defined here as the magnitude of the effect produced by a given amount of drug, as demonstrated in placebo control trials; i.e., the effectiveness per unit dose. DATA SYNTHESIS: Treatment guidelines categorize patients by their risk of coronary events and set lower target cholesterol levels for patients at higher risk. Statins vary in their efficacy. If effectiveness is expressed as percent lowering in low-density lipoprotein cholesterol (LDL-C) and relatively little cholesterol lowering is required as in low-risk patients even statins of low efficacy provide adequate cholesterol lowering, and drug price is the determining factor of cost effectiveness. For patients at high risk the primary target group, which has been expanded in recent guidelines high-efficacy statins are required to meet the more aggressive cholesterol goals, and efficacy is the important determinant of cost-effectiveness. When effectiveness is expressed in terms of life-years saved, the cost-effectiveness of statins as a class for treatment of high-risk patients compares favorably with the cost-effectiveness of generally accepted medical treatments. CONCLUSIONS: In order to optimize cost-effectiveness, the level of effectiveness required to treat the specific patient or patient group must be considered. Statin efficacy is the major determinant of cost-effectiveness when greater cholesterol lowering is required, i.e., for high-risk patients, who make up the primary target group. Statin price is the more important factor if only limited cholesterol lowering (e.g., 35% or less reduction in LDL) is required.
Mind-reading without the scanner: Behavioural decoding of working memory content

ABSTRACT Sophisticated machine learning algorithms have been successfully applied to functional neuroimaging data in order to characterize internal cognitive states. But is it possible to “mind-read” without the scanner? Capitalizing on the robust finding that the contents of working memory guide visual attention toward memory-matching objects, we trained a multivariate pattern classifier on behavioural indices of attentional guidance. Working memory representations were successfully decoded from behaviour alone, both within and between individuals. The current study provides a proof-of-concept for applying machine learning techniques to simple behavioural outputs (e.g., response times) in order to decode information about specific internal cognitive states.