Kilo-instruction processors: overcoming the memory wall

Historically, advances in integrated circuit technology have driven improvements in processor microarchitecture and led to todays microprocessors with sophisticated pipelines operating at very high clock frequencies. However, performance improvements achievable by high-frequency microprocessors have become seriously limited by main-memory access latencies because main-memory speeds have improved at a much slower pace than microprocessor speeds. Its crucial to deal with this performance disparity, commonly known as the memory wall, to enable future high-frequency microprocessors to achieve their performance potential. To overcome the memory wall, we propose kilo-instruction processors-superscalar processors that can maintain a thousand or more simultaneous in-flight instructions. Doing so means designing key hardware structures so that the processor can satisfy the high resource requirements without significantly decreasing processor efficiency or increasing energy consumption.Peer ReviewedPostprint (published version

A Budget Impact and Cost-Effectiveness Analysis of Blood Glucose Monitoring System in One Italian Region

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Runahead threads to improve SMT performance

In this paper, we propose Runahead Threads (RaT) as a valuable solution for both reducing resource contention and exploiting memory-level parallelism in Simultaneous Multithreaded (SMT) processors. Our technique converts a resource intensive memory-bound thread to a speculative light thread under long-latency blocking memory operations. These speculative threads prefetch data and instructions with minimal resources, reducing critical resource conflicts between threads. We compare an SMT architecture using RaT to both state-of-the-art static fetch policies and dynamic resource control policies. In terms of throughput and fairness, our results show that RaT performs better than any other policy. The proposed mechanism improves average throughput by 37% regarding previous static fetch policies and by 28% compared to previous dynamic resource scheduling mechanisms. RaT also improves fairness by 36% and 30% respectively. In addition, the proposed mechanism permits register file size reduction of up to 60% in a SMT processor without performance degradation.Peer ReviewedPostprint (published version

Lung CD57+ cell density is increased in very severe COPD

Among all inflammatory cells involved in COPD, those with a cytolytic or elastolytic activity are thought to play a key role in the pathogenesis of the disease. However, there is no data about the infiltration of cells expressing the CD57 marker in small airways and parenchyma of COPD patients. In this study, surgical specimens from 43 subjects undergoing lung resection due to lung cancer (9 non-smokers, 18 smokers without COPD and 16 smokers with moderate COPD) and 16 patients undergoing double lung transplantation for very severe COPD were examined. CD57+ cells, neutrophils, macrophages and mast cells infiltrating bronchioles (epithelium, smooth muscle and connective tissue) and parenchymal interstitium were localized and quantified by immunohistochemical analysis. Compared to the other groups, the small airways of very severe COPD patients showed a significantly higher density of CD57+ cells, mainly infiltrated in the connective tissue (p=0.001), and a significantly higher density of neutrophils located characteristically in the epithelium (p=0.037). Also, the density of neutrophils was significantly higher in parenchyma of very severe COPD patients compared with the rest of the groups (p=0.001). Finally, there were significant correlations between the bronchiolar density of CD57+ cells and the FEV1 values (R=-0.43, p=0.022), as well as between the parenchymal density of neutrophils and macroscopic emphysema degree (R=0.43, p=0.048) in COPD groups. These results show that CD57+ cells may be involved in COPD pathogenesis, especially in the most severe stages of the disease

Response of fish communities in rivers subjected to a high sediment load

Erosion and sediment yield are a significant problem in the Guadalquivir River basin. Such phenomena are largely driven by a land use devoted to intensive cultivation of olive trees, with a large socioeconomic influence in Andalusia. This sediment overload in rivers causes serious impacts on all fluvial ecosystem components. In this study we assess the chronic effect of sediment yield on fish communities at 104 river sites located in two different sub-catchments ? the Bembézar and Guadajoz rivers ? both with different lithological composition and erosion rates. Sediment yield was estimated using a semi-quantitative Factorial Score Model (FSM), developed specifically for Spanish rivers. The fish populations of both basins were evaluated in composition and abundances by the study of Fernández-Delgado et al., 2014. The influence of sediment yield on the fish community was analyzed using General Additive Models. The sediment yield was higher in the Guadajoz basin (921 T/Km2 per year) than in Bembézar (701 T/Km2 per year). In the former, fish communities were poorer in both fish density and diversity, with Luciobarbus sclateri as the only substantially present species and a significant relationship between sediment yield and load, and fish density. In contrast, in the Bembézar basin, sediment yield was correlated with total fish density, including Luciobarbus sclateri, Pseudochondrostoma willkommii, Cobitis paludica, Iberochondrostoma lemmingii, Anaecypris hispanica, and Cyprinus carpio. Intermediate values of sediment yield led to maximum densities, while those higher decreased the density of these species

Anticipatory reaching of seven- to eleven-month-old infants in occlusion situations

The present study examined 7- to 11-month-old infants' anticipatory and reactive reaching for temporarily occluded objects. Infants were presented with laterally approaching objects that moved at different velocities (10, 20, and 40. cm/s) in different occlusion situations (no-, 20. cm-, and 40. cm-occlusion), resulting in occlusion durations ranging between 0 and 4. s. Results show that except for object velocity and occlusion distance, occlusion duration was a critical constraint for infants' reaching behaviors. We found that the older infants reached more often, but that an increase in occlusion duration resulted in a decline in reaching frequency that was similar across age groups. Anticipatory reaching declined with increasing occlusion duration, but the adverse effects for longer occlusion durations diminished with age. It is concluded that with increasing age infants are able to retain and use information to guide reaching movements over longer periods of non-visibility, providing support for the graded representation hypothesis (Jonsson & von Hofsten, 2003) and the two-visual systems model (Milner & Goodale, 1995). © 2010 Elsevier Inc

Comparison of non-invasive electrohysterographic recording techniques for monitoring uterine dynamics

Non-invasive recording of uterine myoelectric activity (electrohysterogram, EHG) could provide an alternative to monitoring uterine dynamics by systems based on tocodynamometer (TOCO). Laplacian recording of bioelectric signals has been shown to give better spatial resolution and less interference than mono and bipolar surface recordings. The aim of this work was to study the signal quality obtaines from monopolar, bipolar and Laplacian techniques in EHG recordings, as well as to assess their ability to detect uterine contractions. Twenty-two recording sessions were carried out on singleton pregnant women during the active phase of labour. In each session the following simultaneous recordings were obtained: internal uterine pressure (IUP), external tension of abdominal wall (TOCO) and EHG signals (5 monopolar and 4 bipolar recordings, 1 discrete aproximation to the Laplacian of the potential and 2 estimates of the Laplacian from two active annular electrodes). The results obtained show that EHG is able to detect a higher number of uterine contractions than TOCO. Laplacian recordings give improved signal quality over monopolar and bipolar techniques, reduce maternal cardiac interference and improve the signal-to-noise ratio. The optimal position for recording EHG was found to be the uterine median axis and the lower centre-right umbilical zone.Research partly supported by the Spanish Ministerio de Ciencia y Tecnologia (TEC2010-16945) and the Universitat Politecnica de Valencia (PAID 2009/10-2298). The translation of this paper was funded by the Universitat Politecnica de Valencia, Spain.Alberola Rubio, J.; Prats Boluda, G.; Ye Lin, Y.; Valero, J.; Perales Marin, AJ.; Garcia Casado, FJ. (2013). Comparison of non-invasive electrohysterographic recording techniques for monitoring uterine dynamics. Medical Engineering and Physics. 35(12):1736-1743. https://doi.org/10.1016/j.medengphy.2013.07.008S17361743351

Prediction of labor onset type: Spontaneous vs induced; role of electrohysterography?

Background and objective Induction of labor (IOL) is a medical procedure used to initiate uterine contractions to achieve delivery. IOL entails medical risks and has a significant impact on both the mother's and newborn's well-being. The assistance provided by an automatic system to help distinguish patients that will achieve labor spontaneously from those that will need late-term IOL would help clinicians and mothers to take an informed decision about prolonging pregnancy. With this aim, we developed and evaluated predictive models using not only traditional obstetrical data but also electrophysiological parameters derived from the electrohysterogram (EHG). Methods EHG recordings were made on singleton term pregnancies. A set of 10 temporal and spectral parameters was calculated to characterize EHG bursts and a further set of 6 common obstetrical parameters was also considered in the predictive models design. Different models were implemented based on single layer Support Vector Machines (SVM) and with aggregation of majority voting of SVM (double layer), to distinguish between the two groups: term spontaneous labor (≤41 weeks of gestation) and IOL late-term labor. The areas under the curve (AUC) of the models were compared. Results The obstetrical and EHG parameters of the two groups did not show statistically significant differences. The best results of non-contextualized single input parameter SVM models were achieved by the Bishop Score (AUC = 0.65) and GA at recording time (AUC = 0.68) obstetrical parameters. The EHG parameter median frequency, when contextualized with the two obstetrical parameters improved these results, reaching AUC = 0.76. Multiple input SVM obtained AUC = 0.70 for all EHG parameters. Aggregation of majority voting of SVM models using contextualized EHG parameters achieved the best result AUC = 0.93. Conclusions Measuring the electrophysiological uterine condition by means of electrohysterographic recordings yielded a promising clinical decision support system for distinguishing patients that will spontaneously achieve active labor before the end of full term from those who will require late term IOL. The importance of considering these EHG measurements in the patient's individual context was also shown by combining EHG parameters with obstetrical parameters. Clinicians considering elective labor induction would benefit from this technique.General Electric HealthcareAlberola Rubio, J.; Garcia Casado, FJ.; Prats-Boluda, G.; Ye Lin, Y.; Desantes, D.; Valero, J.; Perales Marin, AJ. (2017). Prediction of labor onset type: Spontaneous vs induced; role of electrohysterography?. Computer Methods and Programs in Biomedicine. 144:127-133. https://doi.org/10.1016/j.cmpb.2017.03.018S12713314

Metallofluorescent Nanoparticles for Multimodal Applications

Herein, we describe the synthesis and application of cross-linked polystyrene-based dual-function nano- and microparticles containing both fluorescent tags and metals. Despite containing a single dye, these particles exhibit a characteristic dual-band fluorescence emission. Moreover, these particles can be combined with different metal ions to obtain hybrid metallofluorescent particles. We demonstrate that these particles are easily nanofected into living cells, allowing them to be used for effective fingerprinting in multimodal fluorescence-based and mass spectrometry-based flow cytometry experiments. Likewise, the in situ reductions of the metal ions enable other potential uses of the particles as heterogeneous catalysts

Levels of ADAM10 are reduced in Alzheimer's disease CSF

BACKGROUND: The disintegrin metalloproteinase 10 (ADAM10) is the main α-secretase acting in the non-amyloidogenic processing of the amyloid precursor protein. This study assesses whether ADAM10 is present in cerebrospinal fluid (CSF), and whether it has potential as a biomarker for Alzheimer’s disease (AD). METHODS: ADAM10 was characterized in human CSF samples by immunoprecipitation and western blotting using antibodies specific for different domains of the protein and by ultracentrifugation in sucrose density gradients. Samples from AD patients (n = 20) and age-matched non-AD controls (n = 20) were characterized for classical CSF biomarkers, Aβ42, T-tau, or P-tau by ELISA, and assayed for soluble ADAM10 levels by western blotting. RESULTS: We found that ADAM10 is present in human CSF as several distinct species: an immature form retaining the prodomain (proADAM10; ~ 80 kDa), a mature unprocessed full-length form (ADAM10f; ~ 55 kDa), and a truncated large soluble form released from the membrane (sADAM10; ~ 50 kDa). Fractionation by ultracentrifugation on sucrose density gradients showed that the ADAM10f and sADAM10 species form large complexes. Immunoblotting revealed a significant decrease in ADAM10f and sADAM10 in AD CSF compared to control CSF, while proADAM10 levels remained unaltered. CONCLUSIONS: Several forms of ADAM10 are present in CSF, mainly assembled as high-molecular weight complexes. The determination of the levels of mature forms of CSF-ADAM10 may be useful as a biomarker for AD