A Posture Sequence Learning System for an Anthropomorphic Robotic Hand

The paper presents a cognitive architecture for posture learning of an anthropomorphic robotic hand. Our approach is aimed to allow the robotic system to perform complex perceptual operations, to interact with a human user and to integrate the perceptions by a cognitive representation of the scene and the observed actions. The anthropomorphic robotic hand imitates the gestures acquired by the vision system in order to learn meaningful movements, to build its knowledge by different conceptual spaces and to perform complex interaction with the human operator

Hyperhomocysteinemia: related genetic diseases and congenital defects, abnormal DNA methylation and newborn screening issues

Homocysteine, a sulfur-containing amino acid derived from the methionine metabolism, is located at the branch point of two pathways of the methionine cycle, i.e. remethylation and transsulfuration. Gene abnormalities in the enzymes catalyzing reactions in both pathways lead to hyperhomocysteinemia. Hyperhomocysteinemia is associated with increased risk for congenital disorders, including neural tube closure defects, heart defects, cleft lip/palate, Down syndrome, and multi-system abnormalities in adults. Since hyperhomocysteinemia is known to affect the extent of DNA methylation, it is likely that abnormal DNA methylation during embryogenesis, may be a pathogenic factor for these congenital disorders. In this review we highlight the importance of homocysteinemia by describing the genes encoding for enzymes of homocysteine metabolism relevant to the clinical practice, especially cystathionine-β-synthase and methylenetetrahydrofolate reductase mutations, and the impairment of related metabolites levels. Moreover, a possible correlation between hyperhomocysteine and congenital disorders through the involvement of abnormal DNA methylation during embryogenesis is discussed. Finally, the relevance of present and future diagnostic tools such as tandem mass spectrometry and next generation sequencing in newborn screening is highlighted

Crossing the Abyss: A Comparative Analysis of the Enforceability of Preliminary Agreements

A major unresolved issue in international business transactions relates to the enforceability of preliminary agreements. Preliminary agreements cover a long list of instruments commonly used in most sectors of the economy. The common presumption is that these agreements are not enforceable. The correct answer is much more nuanced. For example, a preliminary agreement may be held to be unenforceable but at the same time be the basis for legal liability. There are strong differences between the civil and common laws on the issues of good faith negotiations and the enforceability of preliminary agreements, but there is also sustained uncertainty within legal systems. This article reviews Chinese, French, German, and Anglo-American law on the twin issues of enforceability and liability. It shows that the trend has been in favor of greater judicial scrutiny of such agreements that has led to greater enforceability and the expansion of available remedies, whether an agreement is deemed to be enforceable or unenforceable. The issue of preliminary agreements and their place in the overall legal scheme has become less clear as courts have recognized their necessity as modern contract transactions have become more long-term and complex. The countries selected for review provide a three-part taxonomy. First, preliminary agreements are unenforceable due to the lack of certainty of terms and party intent. Second, preliminary agreements that are detailed may be recognized as enforceable contracts. Third, there is a broad middle area in which preliminary agreements are unenforceable as a whole but can be the basis for liability for independent obligations found in the agreements. These independent obligations include an implied-in-law or an implied-in-fact obligation to negotiate in good faith, duty of confidentiality, and duty of exclusivity to not negotiate with other parties. It is in this middle area where there has been a convergence in legal systems and, at the same time, where the issues of liability and remedies have become more uncertain. Because of the ubiquity of these agreements, the possibility of unexpected liability remains pronounced in international business negotiations

Detection, characterization and sizing of hydrogen induced cracking in pressure vessels using phased array ultrasonic data processing

Pressure vessels operating in sour service conditions in refinery environments can be subject to the risk of H₂S cracking resulting from the hydrogen entering into the material. This risk, which is related to the specific working conditions and to the quality of the steel used, shall be properly managed in order to maintain the highest safety at a cost-effective level. Nowadays the typical management strategy is based on a risk based inspection (RBI) evaluation to define the inspection plan used in conjunction with a fitness for service (FFS) approach in defining if the vessel, although presenting dangerous defects such as cracks, can still be considered “fit for purpose” for a given time window based on specific fracture mechanics analysis. These vessels are periodically subject to non-destructive evaluation, typically ultrasonic testing. Phased Array (PA) ultrasonic is the latest technology more and more used for this type of application. This paper presents the design and development of an optimized Phased Array ultrasonic inspection technique for the detection and sizing of hydrogen induced cracking (HIC) type flaws used as reference for comparison. Materials used, containing natural operational defects, were inspected in “as-service” conditions. Samples have then been inspected by means of a “full matrix capture” (FMC) acquisition process followed by “total focusing method” (TFM) data post processing. FCM-TFM data have been further post-processed and then used to create a 3D geometrical reconstruction of the volume inspected. Results obtained show the significant improvement that FMC/TFM has over traditional PA inspection techniques both in terms of sensitivity and resolution for this specific type of defect. Moreover, since the FMC allows for the complete time domain signal to be captured from every element of a linear array probe, the full set of data is available for post-processing. Finally, the possibility to reconstruct the geometry of the component from the scans, including the defects present in its volume, represents the ideal solution for a reliable data transferring process to the engineering function for the subsequent FFS analysi

Heat shock affects mitotic segregation of human chromosomes bound to stress-induced satellite III RNAs

Heat shock activates the transcription of arrays of Satellite III (SatIII) DNA repeats in the pericentromeric heterochromatic domains of specific human chromosomes, the longest of which is on chromosome 9. Long non-coding SatIII RNAs remain associated with transcription sites where they form nuclear stress bodies or nSBs. The biology of SatIII RNAs is still poorly understood. Here, we show that SatIII RNAs and nSBs are detectable up to four days after thermal stress and are linked to defects in chromosome behavior during mitosis. Heat shock perturbs the execution of mitosis. Cells reaching mitosis during the first 3 h of recovery accumulate in pro-metaphase. During the ensuing 48 h, this block is no longer detectable; however, a significant fraction of mitoses shows chromosome segregation defects. Notably, most of lagging chromosomes and chromosomal bridges are bound to nSBs and contain arrays of SatIII DNA. Disappearance of mitotic defects at the end of day 2 coincides with the processing of long non-coding SatIII RNAs into a ladder of small RNAs associated with chromatin and ranging in size from 25 to 75 nt. The production of these molecules does not rely on DICER and Argonaute 2 components of the RNA interference apparatus. Thus, massive transcription of SatIII DNA may contribute to chromosomal instability

Cancer cell metabolism in hypoxia: Role of HIF-1 as key regulator and therapeutic target

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underlies the metabolic and functional changes of cancer cells. Noteworthy, HIF-1 represents a promising target for novel cancer therapeutics. In this review, we summarize the molecular mechanisms underlying the interplay between HIF-1 and energetic metabolism, with a focus on mitochondria, of hypoxic cancer cells

Monte-Carlo simulation with FLUKA for liquid and solid targets

Introduction Monte-Carlo simulations can be used to assess isotope production on small medical cyclotrons. These simulations calculate the particle interactions with electric and magnetic fields, as well as the nuclear reactions. The results can be used to predict both yields and isotopic contaminations and can aid in the optimum design of target material and target geometry [1,2]. FLUKA is a general-purpose tool widely used in many applications from accelerator shielding to target design, calorimetry, activation, dosimetry, detector design, neutrino physics, or radiotherapy [3,4]. In this work, we applied the Monte-Carlo code FLUKA to determine the accuracy of predicting yields of various isotopes as compared to experimental yields. Material and Methods The proton beam collimation system, as well as the liquid and solid target of the TR13 cyclotron at TRIUMF, has been modeled in FLUKA. The proton beam parameters were initially taken from the cyclotron design specifications and were optimized against experimental measurements from the TR13. Data from irradiations of different targets and with different beam currents were collected in order to account for average behavior, see FIG. 1. Yields for a pencil proton beam as well as a beam spread out in direction and energy have been calculated and have been compared to experimental results obtained with the TR13. Results and Conclusion The reactions listed in TABLE 1 were assessed. For most reactions a good agreement was found in the comparison between experimental and simulated saturation yield. TABLE 1 only shows the yields simulated with a proton beam with a spread in both direction and energy. In most cases, the simulated yield is slightly larger or comparable. Only the calculated yield for 55Co was significantly lower by a factor of 4.2. This is still a good agreement considering that FLUKA was originally a high-energy physics code. It may indicate that the FLUKA internal cross-section calculation for this isotope production needs some optimization. In summary, we conclude that FLUKA can be used as a tool for the prediction of isotope production as well as for target design

A key role of the mitochondrial citrate carrier (SLC25A1) in TNFα- and IFNγ-triggered inflammation

The chronic induction of inflammation underlies multiple pathological conditions, including metabolic, autoimmune disorders and cancer. The mitochondrial citrate carrier (CIC), encoded by the SLC25A1 gene, promotes the export of citrate from the mitochondria to the cytoplasm, a process that profoundly influences energy balance in the cells. We have previously shown that SLC25A1 is a target gene for lipopolysaccharide signaling and promotes the production of inflammatory mediators. We now demonstrate that SLC25A1 is induced at the transcriptional level by two key pro-inflammatory cytokines, tumor necrosis factor-α (TNFα) and interferon-γ (IFNγ), and such induction involves the activity of the nuclear factor kappa B and STAT1 transcription factors. By studying the down-stream events following SLC25A1 activation during signals that mimic inflammation, we demonstrate that CIC is required for regulating the levels of nitric oxide and of prostaglandins by TNFα or IFNγ. Importantly, we show that the citrate exported from mitochondria via CIC and its downstream metabolic intermediate, acetyl-coenzyme A, are necessary for TNFα or IFNγ to induce nitric oxide and prostaglandin production. These findings provide the first line of evidence that the citrate export pathway, via CIC, is central for cytokine-induced inflammatory signals and shed new light on the relationship between energy metabolism and inflammation