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

TOpic: rare and special cases, the real "Strange cases"

Introduction: The bladder hernia represents approximately 1-3% of all inguinal hernias, where patients aged more than 50 years have a higher incidence (10%). Many factors contribute to the development of a bladder hernia, including the presence of a urinary outlet obstruction causing chronic bladder distention, the loss of bladder tone, pericystitis, the perivesical bladder fat protrusion and the obesity

Characteristics of patients making serious inhaler errors with a dry powder inhaler and association with asthma-related events in a primary care setting

Acknowledgements The iHARP database was funded by unrestricted grants from Mundipharma International Ltd and Research in Real-Life Ltd; these analyses were funded by an unrestricted grant from Teva Pharmaceuticals. Mundipharma and Teva played no role in study conduct or analysis and did not modify or approve the manuscript. The authors wish to direct a special appreciation to all the participants of the iHARP group who contributed data to this study and to Mundipharma, sponsors of the iHARP group. In addition, we thank Julie von Ziegenweidt for assistance with data extraction and Anna Gilchrist and Valerie L. Ashton, PhD, for editorial assistance. Elizabeth V. Hillyer, DVM, provided editorial and writing support, funded by Research in Real-Life, Ltd.Peer reviewedPublisher PD

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

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

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