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Technological advances in massively parallel sequencing have led to an exponential growth in the number of known protein sequences. Much of this growth originates from metagenomic projects producing new sequences from environmental and clinical samples. The Unified Human Gastrointestinal Proteome (UHGP) catalogue is one of the most relevant metagenomic datasets with applications ranging from medicine to biology. However, the lack of sequence annotation impairs its usability. This work aims to produce a family classification of UHGP sequences to facilitate downstream structural and functional annotation. This is achieved through the release of theDPCfam-UHGP50 datasetcontaining 10,778 putative protein families generated using DPCfam clustering, an unsupervised pipeline grouping sequences into multi-domain architectures. DPCfam-UHGP50 considerably improves family coverage at protein and residue levels compared to the manually curated repository Pfam. It is our hope that DPCfam-UHGP50 will foster future discoveries in the field of metagenomics of the human gut by the release of a FAIR-compliant database easily accessible via a searchable web server and Zenodo repository.

The Backpropagation algorithm, widely used to train neural networks, has often been criticised for its lack of biological realism. In an attempt to find a more biologically plausible alternative, and avoid to back-propagate gradients in favour of using local learning rules, the recently introduced Forward-Forward algorithm replaces the traditional forward and backward passes of Backpropagation with two forward passes. In this work, we show that internal representations obtained with the Forward-Forward algorithm organize into robust, category-specific ensembles, composed by an extremely low number of active units (high sparsity). This is remarkably similar to what is observed in cortical representations during sensory processing. While not found in models trained with standard Backpropagation, sparsity emerges also in networks optimized by Backpropagation, on the same training objective of Forward-Forward. These results suggest that the learning procedure proposed by Forward-Forward may be superior to Backpropagation in modelling learning in the cortex, even when a backward pass is used., Comment: 14 pages, 8 figures

Bardet–Biedl syndrome is a rare autosomal recessive disorder characterized by rod-cone dystrophy, renal dysfunction, obesity, learning difficulties, hypogonadism, polydactyl, and many other minor features that can affect the cardiovascular, locomotive, neurological, and endocrine systems. We report the case of a 16-year-old boy affected by Bardet–Biedl syndrome who presented with recurrent pericarditis with an optimal response to treatment with Anakinra. To our knowledge, this is the first description of an association between Bardet–Biedl syndrome and recurrent pericarditis.

Protein language models (pLMs) transform their input into a sequence of hidden representations whose geometric behavior changes across layers. Looking at fundamental geometric properties such as the intrinsic dimension and the neighbor composition of these representations, we observe that these changes highlight a pattern characterized by three distinct phases. This phenomenon emerges across many models trained on diverse datasets, thus revealing a general computational strategy learned by pLMs to reconstruct missing parts of the data. These analyses show the existence of low-dimensional maps that encode evolutionary and biological properties such as remote homology and structural information. Our geometric approach sets the foundations for future systematic attempts to understand thespaceof protein sequences with representation learning techniques.

Atrial Fibrillation (AF) is a heart's arrhythmia which, despite being often asymptomatic, represents an important risk factor for stroke, therefore being able to predict AF at the electrocardiogram exam, would be of great impact on actively targeting patients at high risk. In the present work we use Convolution Neural Networks to analyze ECG and predict Atrial Fibrillation starting from realistic datasets, i.e. considering fewer ECG than other studies and extending the maximal distance between ECG and AF diagnosis. We achieved 75.5% (0.75) AUC firstly increasing our dataset size by a shifting technique and secondarily using the dilation parameter of the convolution neural network. In addition we find that, contrarily to what is commonly used by clinicians reporting AF at the exam, the most informative leads for the task of predicting AF are D1 and avR. Similarly, we find that the most important frequencies to check are in the range of 5-20 Hz. Finally, we develop a net able to manage at the same time the electrocardiographic signal together with the electronic health record, showing that integration between different sources of data is a profitable path. In fact, the 2.8% gain of such net brings us to a 78.6% (std 0.77) AUC. In future works we will deepen both the integration of sources and the reason why we claim avR is the most informative lead., Comment: 10 pages, 2 figures, 5 tables

Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder. When it presents before the age of 18 years (childhood-onset systemic lupus erythematosus, cSLE), the disease course tends to be more severe with a higher rate of organ involvement and requires an early diagnosis. Gastrointestinal involvement in cSLE is rare and scarcely reported in the literature. Any organ of the gastrointestinal system may be affected, either as a direct consequence of the disease, as a subsequent complication, or as an adverse drug event. Abdominal pain is the most common GI symptom, it can be diffuse or well localized, and can underline different conditions such as hepatitis, pancreatitis, appendicitis, peritonitis, or enteritis. cSLE may have an alteration of the intestinal barrier with features of protein-losing enteropathy or, in genetically predisposed patients, may develop associated autoimmune disorders such as Coeliac Disease or Autoimmune Hepatitis. The aim of this manuscript is to provide a narrative review of gastrointestinal manifestations in cSLE focused on hepatic, pancreatic, and intestinal involvement. A comprehensive literature search based on the PubMed database was performed.

Significance A major challenge in studying intention reading is high motor variability. Analyses conducted across trials provide insights into what happens on average; however, they may obscure how individual observers read intention information in individual movements. We combined motion tracking, psychophysics, and computational analyses to examine intention reading in autism spectrum disorders (ASDs) with single-trial resolution. Results revealed that a sizeable fraction of ASD observers can identify intention-informative variations in ASD (but not in typically developing) movement kinematics, but they are nonetheless unable to extract the encoded intention information. This approach not only enhances our basic understanding of mind reading in ASD but also provides potential avenues for the rational design of training procedures to improve the reading of others’ actions.

Failure to develop prospective motor control has been proposed to be a core phenotypic marker of autism spectrum disorders (ASD). However, whether genuine differences in prospective motor control permit discriminating between ASD and non-ASD profiles over and above individual differences in motor output remains unclear. Here, we combined high precision measures of hand movement kinematics and rigorous machine learning analyses to determine the true power of prospective movement data to differentiate children with autism and typically developing children. Our results show that while movement is unique to each individual, variations in the kinematic patterning of sequential grasping movements genuinely differentiate children with autism from typically developing children. These findings provide quantitative evidence for a prospective motor control impairment in autism and indicate the potential to draw inferences about autism on the basis of movement kinematics.

Professional magicians regularly use pantomimed grasps (i.e., movements towards imagined objects) to deceive audiences. To do so, they learn to shape their hands similarly for real and pantomimed grasps. Here we tested whether this form of motor expertise provides them a significant benefit when processing pantomimed grasps. To this aim, in a one-interval discrimination design, we asked 17 professional magicians and 17 naïve controls to watch video clips of reach-to-grasp movements recorded from naïve participants and judge whether the observed movement was real or pantomimed. All video clips were edited to spatially occlude the grasped object (either present or imagined). Data were analysed within a drift diffusion model approach. Fitting different models showed that, whereas magicians and naïve performed similarly when observing real grasps, magicians had a specific advantage compared with naïve at discriminating pantomimed grasps. These findings suggest that motor expertise may be crucial for detecting relevant cues from hand movement during the discrimination of pantomimed grasps. Results are discussed in terms of motor recalibration.

Deep convolutional networks (DCNs) learn meaningful representations where data that share the same abstract characteristics are positioned closer and closer. Understanding these representations and how they are generated is of unquestioned practical and theoretical interest. In this work we study the evolution of the probability density of the ImageNet dataset across the hidden layers in some state-of-the-art DCNs. We find that the initial layers generate a unimodal probability density getting rid of any structure irrelevant for classification. In subsequent layers density peaks arise in a hierarchical fashion that mirrors the semantic hierarchy of the concepts. Density peaks corresponding to single categories appear only close to the output and via a very sharp transition which resembles the nucleation process of a heterogeneous liquid. This process leaves a footprint in the probability density of the output layer where the topography of the peaks allows reconstructing the semantic relationships of the categories.

Is it possible to perceive others' mental states? Are mental states visible in others' behavior? In contrast to the traditional view that mental states are hidden and not directly accessible to perception, in recent years a phenomenologically-motivated account of social cognition has emerged: direct social perception. However, despite numerous published articles that both defend and critique direct perception, researchers have made little progress in articulating the conditions under which direct perception of others' mental states is possible. This paper proposes an empirically anchored approach to the observability of others' mentality - not just in the weak sense of discussing relevant empirical evidence for and against the phenomenon of interest, but also, and more specifically, in the stronger sense of identifying an experimental strategy for measuring the observability of mental states and articulating the conditions under which mental states are observable. We conclude this article by reframing the problem of direct perception in terms of establishing a definable and measurable relationship between movement features and perceived mental states.

Introduction Psychosocial factors play an important role in non-communicable diseases (NCDs). This observational study is primarily aimed at assessing the relationship of psychological characteristics of patients with the outcomes of different NCDs, and to assess short-term psychotherapy (STP) efficacy in the real world. Methods: One hundred and forty patients with recent acute myocardial infarction, Takotsubo syndrome, or non-metastatic breast cancer and a control group of 140 age and sex-matched healthy subjects, will be enrolled. All subjects will be administered psychometric tests, quality of life tests, a specific body perception questionnaire, a dream questionnaire, and a projective test, the Six Drawing test at baseline and follow-up. All subjects with medical conditions will be asked to freely choose between an ontopsychological STP along with standard medical therapy and, whenever indicated, rehabilitation therapy or medical therapy plus rehabilitation alone. The study endpoints will be to evaluate: the relationship of the psychological characteristics of enrolled subjects with the outcomes of different NCDs, predictors of the choice of psychotherapy, and the efficacy of ontopsychological intervention on psychological and medical outcomes. Conclusion: This study will generate data on distinctive psychological characteristics of patients suffering from different CDs and their relationship with medical outcomes, as well as explore the efficacy of ontopsychological STP in these patients in the real world. (Number of registration: NCT03437642).

Highlights • Observation of others’ actions provides a shared experience of objects acted upon. • Observation of grasping movements provides a shared experience of object weight. • Object weight can be predictively judged from the kinematics of real grasps. • Weight judgements are also possible from the observation of pantomimed grasps., Observation of others’ actions has been proposed to provide a shared experience of the properties of objects acted upon. We report results that suggest a similar form of shared experience may be gleaned from the observation of pantomimed grasps, i.e., grasps aimed at pretended objects. In a weight judgment task, participants were asked to observe a hand reaching towards and grasping either a real or imagined glass, and to predictively judge its weight. Results indicate that participants were able to discriminate whether the to-be-grasped glass was empty, and thus light, or full, and thus heavy. Worthy of further investigation, this finding suggests that by observing others’ movements we can make predictions, and form expectations about the characteristics of objects that exist only in others’ minds.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease characterized by multiple and bilateral cystic dilation of renal tubules. Hypertension, endothelial dysfunction, systemic inflammation, and accelerated atherosclerosis are alterations found at a very early stage of the disease and are responsible for increasing both cardiovascular risks and progression toward end-stage renal disease. The aim of the study was to evaluate the effects of the use of 1.6 g α-lipoic acid (ALA) daily for 3 and 6 on the main markers of systemic inflammation, endothelial dysfunction, and atherosclerosis, as well as on nutritional, cardiovascular, and psychocognitive parameters, in ADPKD patients with CKD stage G2/G3 Kidney Disease Improving Global Outcomes chronic kidney disease (KDIGO) compared to controls.This was a controlled, longitudinal, prospective, interventional study with 59 patients with ADPKD. Of the patients, 33 were treated with ALA (1.6 g/d) for 6 mo and 26 were controls. Clinical, laboratory (inflammation and metabolic indexes), instrumental parameters (intima media thickness (IMT), renal resistive index (RRI), flow-mediated dilation (FMD), ankle-brachial index (ABI), and psycho-cognitive tests (Mini-Mental State Examination [MMSE], Hamilton Depression Rating Scale [HAM-D], Beck Depression Inventory-II [BDI-II]) were evaluated at baseline (T0), 3 mo (T1), and 6 mo (T2).Patients treated with ALA at T1 and T2 showed a significant reduction in serum glucose, insulin, homeostatic model assessment-insulin resistance, and serum uric acid (P = 0.013, P = 0.002, P = 0.002, P0.001; respectively) and significantly higher values of base excess (P0.001), compared with the control group. Moreover, the results showed a significant increase in bicarbonates (P = 0.009) and FMD (P0.001), and a significant reduction of C-reactive protein (P0.001) and RRI (P = 0.013). On the other hand, we did not assess a significant difference in IMT and ABI at T1 and T2. Psychocognitive tests (BDI-II, HAM-D, and MMSE) were significantly improved (P = 0.007, P0.001, P0.001; respectively) in patients treated with ALA for 6 mo compared with the control group. A significant difference in nicotinamide adenine dinucleotide phosphate oxidase 2 concentrations was observed between T0 and T2 only in ADPKD patients treated with ALA (P = 0.039, P = 0.039; respectively), although we did not find a significant difference in interleukin-6, interleukin -1β, and tumor necrosis factor-α concentrations in either group.We suggest an early and careful monitoring of traditional and non-traditional cardiovascular risk factors in patients with ADPKD. Moreover, we suggest the use of ALA, an anti-inflammatory and antioxidant nutraceutical with few side effects. Additionally, it is important to evaluate the cognitive abilities, psychological health, and quality of life of patients with ADPKD, especially at the early stage of disease.

On many occasions, people spontaneously or deliberately take the perspective of a person facing them rather than their own perspective. How is this done? Using a spatial perspective task in which participants were asked to identify objects at specific locations, we found that self-perspective judgments were faster for objects presented to the right, rather than the left, and for objects presented closer to the participants’ own bodies. Strikingly, taking the opposing perspective of another person led to a reversal (i.e., remapping) of these effects, with reference to the other person’s position (Experiment 1). A remapping of spatial relations was also observed when an empty chair replaced the other person (Experiment 2), but not when access to the other viewpoint was blocked (Experiment 3). Thus, when the spatial scene allows a physically feasible but opposing point of view, people respond as if their own bodies were in that place. Imagination can thus overcome perception.

During reach-to-grasp movements, the hand is gradually molded to conform to the size and shape of the object to be grasped. Yet the ability to glean information about object properties by observing grasping movements is poorly understood. In this study, we capitalized on the effect of object size to investigate the ability to discriminate the size of an invisible object from movement kinematics. The study consisted of 2 phases. In the first action execution phase, to assess grip scaling, we recorded and analyzed reach-to-grasp movements performed toward differently sized objects. In the second action observation phase, video clips of the corresponding movements were presented to participants in a two-alternative forced-choice task. To probe discrimination performance over time, videos were edited to provide selective vision of different periods from 2 viewpoints. Separate analyses were conducted to determine how the participants' ability to discriminate between stimulus alternatives (Type I sensitivity) and their metacognitive ability to discriminate between correct and incorrect responses (Type II sensitivity) varied over time and viewpoint. We found that as early as 80 ms after movement onset, participants were able to discriminate object size from the observation of grasping movements delivered from the lateral viewpoint. For both viewpoints, information pickup closely matched the evolution of the hand's kinematics, reaching an almost perfect performance well before the fingers made contact with the object (60% of movement duration). These findings suggest that observers are able to decode object size from kinematic sources specified early on in the movement. (PsycINFO Database Record

Recent years have seen accumulating evidence for the proposition that people process time by mapping it onto a linear spatial representation and automatically “project” themselves on an imaginedmental time line. Here, we ask whether people can adopt the temporal perspective of another person when travelling through time. To elucidate similarities and differences between time travelling from one’s own perspective or from the perspective of another person, we asked participants to mentally project themselves or someone else (i.e., a coexperimenter) to different time points. Three basic properties of mental time travel were manipulated: temporal location (i.e., where in time the travel originates: past, present, and future), motion direction (either backwards or forwards), and temporal duration (i.e., the distance to travel: one, three, or five years). We found that time travels originating in the present lasted longer in the self- than in the other-perspective. Moreover, for self-perspective, but not for other-perspective, time was differently scaled depending on where in time the travel originated. In contrast, when considering the direction and the duration of time travelling, no dissimilarities between the self- and the other-perspective emerged. These results suggest that self- and other-projection, despite some differences, share important similarities in structure.

Disturbance of primary prospective motor control has been proposed to contribute to faults in higher mind functions of individuals with autism spectrum disorder, but little research has been conducted to characterize prospective control strategies in autism. In the current study, we applied pattern-classification analyses to kinematic features to verify whether children with autism spectrum disorder (ASD) and typically developing (TD) children altered their initial grasp in anticipation of self- and other-actions. Results indicate that children with autism adjusted their behavior to accommodate onward actions. The way they did so, however, varied idiosyncratically from one individual to another, which suggests that previous characterizations of general lack of prospective control strategies may be overly simplistic. These findings link abnormalities in anticipatory control with increased variability and offer insights into the difficulties that individuals with ASD may experience in social interaction.

Autism is a behavioral neurological disorder affecting a significant percentage of worldwide population. It especially starts manifesting at very low ages, but it is difficult to early diagnose it since there is not a specific exam or trial that is able to spot it safely. Its detection is in fact mainly dependent from the medical expertise used to assess the patient behavior during direct interviews. This work aims at providing an automatic objective support to the doctor for the assessment of (early) diagnosis of possible autistic subjects by only using video sequences. The underlying idea and rationale come from the psychological and neuroscience studies claiming that the executions of simple motor acts are different between pathological and healthy subjects, and this can be sufficient to discriminate between them. To this end, we devised an experiment in which we recorded, using a standard video camera, patient and healthy children performing the same simple gesture of grasping a bottle. By only processing the video clips depicting the grasping action using a recurrent deep neural network, we are able to discriminate with a good accuracy between the 2 classes of subjects. The designed deep model is also able to provide a sort of attention map in which the zones in the video of major interest are identified in space and time: this “explains” in a certain way which areas the model deems more relevant to the classification purpose, which could also be used by the doctor to make the diagnosis. In the end, this work constitutes a first step towards the development of an automatic computational system devoted to the early diagnosis of autistic subjects, providing the medical expert of a supportive objective method, potentially simple to use in clinical and also more open settings.

We explore the use of Intrinsic Dimension (ID) for gaining insights in how populations evolve in Evolutionary Algorithms. ID measures the minimum number of dimensions needed to accurately describe a dataset and its estimators are being used more and more in Machine Learning to cope with large datasets. We postulate that ID can provide information about population which is complimentary w.r.t.\ what (a simple measure of) diversity tells. We experimented with the application of ID to populations evolved with a recent variant of Grammatical Evolution. The preliminary results suggest that diversity and ID constitute two different points of view on the population dynamics., Comment: Evolutionary Machine Learning workshop at International Conference on Parallel Problem Solving from Nature (EML@PPSN), 2018, Coimbra (Portugal)

Is it possible to understand the intentions of others by merely observing their movements? Current debate has been mainly focused on the role that mirror neurons and motor simulation may play in this process, with surprisingly little attention being devoted to how intentions are actually translated into movements. Here, we delineate an alternative approach to the problem of intention-from-movement understanding, which takes “action execution” rather than “action observation” as a starting point. We first consider whether and to what extent, during action execution, intentions shape movement kinematics. We then examine whether observers are sensitive to intention information conveyed by visual kinematics and can use this information to discriminate between different intentions. Finally, we consider the neural mechanisms that may contribute to intention-from-movement understanding. We argue that by reframing the relationship between intention and movement, this evidence opens new perspectives into the neurobiology of how we know other minds and predict others’ behavior.

The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies and is presently being evaluated as an HCV vaccine candidate. HCV binds to human cells through the interaction of E2 with the tetraspanin CD81, a putative viral receptor component. We have analyzed four different E2 proteins from 1a and 1b viral isolates for their ability to bind to recombinant CD81 in vitro and to the native receptor displayed on the surface of Molt-4 cells. A substantial difference in binding efficiency between these E2 variants was observed, with proteins derived from 1b subtypes showing significantly lower binding than the 1a protein. To elucidate the mechanism of E2-CD81 interaction and to identify critical regions responsible for the different binding efficiencies of the E2 variants, several mutants were generated in E2 protein regions predicted by computer modeling to be exposed on the protein surface. Functional analysis of these E2 derivatives revealed that at least two distinct domains are responsible for interaction with CD81. A first segment centered around amino acid residues 613 to 618 is essential for recognition, while a second element including the two hypervariable regions (HVRs) modulates E2 receptor binding. Binding inhibition experiments with anti-HVR monoclonal antibodies confirmed this mapping and supported the hypothesis that a complex interplay between the two HVRs of E2 is responsible for modulating receptor binding, possibly through intramolecular interactions. Finally, E2 proteins from different isolates displayed a profile of binding to human hepatic cells different from that observed on Molt-4 cells or isolated recombinant CD81, indicating that additional factors are involved in viral recognition by target liver cells.

Before a protein vaccine is introduced into a country, it is essential to evaluate its potential impact and estimate its benefits and costs. The aim of this study was to determine the genetic characteristics of Neisseria meningitidis B (NmB) in the pharyngeal secretions of 1375 healthy adolescents aged 13–19 y living in Milan, Italy, in September 2012, and the possible protection offered by the two currently available NmB protein vaccines. Ninety-one subjects were Nm carriers (6.6%), 29 (31.9%) of whom carried the NmB capsular gene. The 29 identified strains belonged to eight clonal complexes (CCs), the majority of which were in the ST-41/44/Lin.3 CC (n = 11; 37.9%). All of the identified strains harboured ƒHbp alleles representing a total of 15 sub-variants: the gene for NHBA protein was found in all but three of the studied strains (10.3%) with 13 identified sub-variants. There were 15 porA sub-types, seven of which were identified in just one CC. The findings of this study seem to suggest that both of the protein vaccines proposed for the prevention of invasive disease due to NmB (the 4-protein and the 2-protein products) have a composition that can evoke a theoretically effective antibody response against the meningococcal strains currently carried by adolescents living in Northern Italy. The genetic characteristics of NmB strains can be easily evaluated by means of molecular methods, the results of which can provide an albeit approximate estimate of the degree of protection theoretically provided by the available vaccines, and the possible future need to change their composition.

We discovered that the hepatitis C virus (HCV) envelope glycoprotein E2 binds to human hepatoma cell lines independently of the previously proposed HCV receptor CD81. Comparative binding studies using recombinant E2 from the most prevalent 1a and 1b genotypes revealed that E2 recognition by hepatoma cells is independent from the viral isolate, while E2–CD81 interaction is isolate specific. Binding of soluble E2 to human hepatoma cells was impaired by deletion of the hypervariable region 1 (HVR1), but the wild-type phenotype was recovered by introducing a compensatory mutation reported previously to rescue infectivity of an HVR1-deleted HCV infectious clone. We have identified the receptor responsible for E2 binding to human hepatic cells as the human scavenger receptor class B type I (SR-BI). E2–SR-BI interaction is very selective since neither mouse SR-BI nor the closely related human scavenger receptor CD36, were able to bind E2. Finally, E2 recognition by SR-BI was competed out in an isolate-specific manner both on the hepatoma cell line and on the human SR-BI-transfected cell line by an anti-HVR1 monoclonal antibody.

On many occasions, people spontaneously or deliberately take the perspective of a person facing them rather than their own perspective. How is this done? Using a spatial perspective task in which participants were asked to identify objects at specific locations, we found that self-perspective judgments were faster for objects presented to the right, rather than the left, and for objects presented closer to the participants' own bodies. Strikingly, taking the opposing perspective of another person led to a reversal (i.e., remapping) of these effects, with reference to the other person's position (Experiment 1). A remapping of spatial relations was also observed when an empty chair replaced the other person (Experiment 2), but not when access to the other viewpoint was blocked (Experiment 3). Thus, when the spatial scene allows a physically feasible but opposing point of view, people respond as if their own bodies were in that place. Imagination can thus overcome perception.

Behavioural and neuropsychological studies suggest that real actions and pantomimed actions tap, at least in part, different neural systems. Inspired by studies showing weight-attunement in real grasps, here we asked whether (and to what extent) kinematics of pantomimed reach-to-grasp movement can reveal the weight of the pretended target. To address this question, we instructed participants (n =15) either to grasp or pretend to grasp towards two differently weighted objects, i.e., a light object and heavy object. Using linear discriminant analysis, we then proceeded to classify the weight of the target – either real or pretended – on the basis of the recorded movement patterns. Classification analysis revealed that pantomimed reach-to-grasp movements retained information about object weight, although to a lesser extent than real grasp movements. These results are discussed in relation to the mechanisms underlying the control of real and pantomimed grasping movements.

The control of indoor thermal comfort in buildings through thermal inertia during the summer season plays a fundamental role in the design of energy efficient buildings, especially in the Mediterranean climate. In fact, lightweight, highly insulated buildings cannot provide the necessary mass to buffer thermal gains. Phase change materials (PCM) have been used to provide lightweight building components with the required thermal inertia without increasing their overall mass. So far the integration of PCM into lightweight piped radiant floors for the control of thermal comfort during summer cooling regimes has not been investigated. This paper reports the development of a lightweight piped radiant floor prototype with an integrated PCM layer aimed at buffering internal gains at constant temperature during summer cooling regimes without affecting its winter warming capacity. Both the construction of the laboratory specimens and the development of the optimized finite element models are detailed and the assessment of the floor performance in a simulated room is discussed.

Interventions directed to the recognition of abnormal bone mineral density, bone mineral content, and body composition in the pediatric age require the definition of factors influencing bone mass acquisition during growth. We have evaluated in a cross-sectional manner by dual-energy X-ray absorptiometry the impact of sex, age, puberty, and physical activity on total body areal bone mineral density, regional (lumbar and femoral) bone mineral densities, bone mineral content, and body composition (fat mass and lean mass) in a cohort of 359 healthy Italian children aged 3-14 years and investigated their specific contribution to bone mass accrual. Statistical multiple regression analysis was performed dividing the population in pre- and post-pubertal groups. Bone mineral density at the lumbar spine has resulted equally distributed in both sexes before puberty while has resulted higher at the femoral necks in males at whatever age. A significant effect on bone mass acquisition was exerted by male sex and lean mass. In the areas where the cortical bone is prevalent, males of the pre-pubertal group have presented the highest values; in the areas where the cancellous bone is prevalent, both sexes were equivalent until the age of 9 years, but after this age, females have presented higher increases, probably related to the inferior dimensional development of lumbar vertebrae. Conclusively, male sex and lean mass seem to represent independent predictors of bone mass accrual in the cortical bone of the examined children, while female sex and pubertal maturation are independent predictors of bone mass accrual in the trabecular bone.

A prototype low-maintenance modular marine cage-culture system for commercial use has been developed and is presently in service at Maine Salmon Farms, Wiscasset, Maine. The basic component of the cage system is a 1 times 3 m fiberglass frame covered with 90/10 copper-nickel expandedmetal mesh of 76% open area. These panels are interconnected along with other fiberglass structurals, fittings and modular float units to form a 57 m3 rigid, floating cage system. The modular design allows this concept to be readily adapted to larger size floating cages, as well as submerged or bottom mounted applications. The excellent engineering properties of 90/10 copper-nickel, coupled with its inherent resistance to biofouling, are the keys to the projected long, useful service life and low maintenance requirements. Design details, performance specifications and economic analysis, for both the prototype and larger future nested commercial systems, are provided.

Previous evidence indicates that, when reaching to grasp a target object, the presence of nontarget irrelevant information (i.e., distractor) presented either in the visual or olfactory modality determines significant interference effects on temporal parameters, such as reaction time and movement time, and on movement kinematics. While research on “visual” distractor has also revealed that such interference effects disappear when prior knowledge about the target is given to participants, this aspect for olfactory distractors has yet to be investigated. Therefore, here we asked participants to reach towards and grasp a small or a large visual target following the delivery of an odor evoking either a small or a large object. When the type of grasp evoked by the odor did not coincide with that for the visual target, interference effects were evident on reach duration and reaction time, but kinematics of hand shaping remained unaltered. This study demonstrates that, when participants knew in advance which object was the target, olfactory nontargets produced no interference effects on movement kinematics, but they did on key temporal measures, i.e., reaction time and reach duration. These findings are discussed in light of current theories put forward to explain the sensory processes underlying the control of action.

The EphA2 receptor tyrosine kinase is overexpressed in a variety of human epithelial cancers and is a determinant of malignant cellular behavior in pancreatic adenocarcinoma cells. Moreover, it is expressed in tumor endothelium and its activation promotes angiogenesis. To better clarify the therapeutic potential of monoclonal antibodies (mAbs) directed to the EphA2 receptor, we generated a large number of mAbs by differential screening of phage-Ab libraries by oligonucleotide microarray technology and implemented a strategy for the rapid identification of antibodies with the desired properties. We selected two high-affinity and highly specific EphA2 monoclonal antibodies with different in vitro properties on the human pancreatic tumor cell line MiaPaCa2. One is a potent EphA2-agonistic antibody, IgG25, that promotes receptor endocytosis and subsequent degradation, and the second is a ligand antagonist, IgG28, that blocks the binding to ephrin A1 and is cross-reactive with the mouse EphA2 receptor. We measured the effect of antibody treatment on the growth of MiaPaCa2 cells orthotopically transplanted in nude mice. Both IgG25 and IgG28 had strong antitumor and antimetastatic efficacy. In vivo treatment with IgG25 determined the reduction of the EphA2 protein levels in the tumor and the phosphorylation of FAK on Tyr576 while administration of IgG28 caused a decrease in tumor vascularization as measured by immunohistochemical analysis of CD31 in tumor sections. These data show that in a pancreatic cancer model comparable therapeutic efficacy is obtained either by promoting receptor degradation or by blocking receptor activation.

We have recently provided evidence for anticipatory grasp control mechanisms in the kinematic domain by showing that subjects modulate digit placement on an object based on its center of mass (CM) when it can be anticipated (Lukos et al., 2007). This behavior relied on sensorimotor memories about digit contact points and forces required for optimal manipulation. We found that accurate sensorimotor memories depended on the acquisition of implicit knowledge about object properties associated with repeated manipulations of the same object.Whereas implicit knowledge of object properties is essential for anticipatory grasp control, the extent to which subjects can use explicit knowledge to accurately scale digit forces in an anticipatory manner is controversial. Additionally, it is not known whether subjects are able to use explicit knowledge of object properties for anticipatory control of contact points. We addressed this question by asking subjects to grasp and lift an object while providing explicit knowledge of object CM location as visual or verbal cues. Contact point modulation and object roll, a measure of anticipatory force control, were assessed using blocked and random CM presentations. We found that explicit knowledge of object CM enabled subjects to modulate contact points. In contrast, subjects could not minimize object roll in the random condition to the same extent as in the blocked when provided with a verbal or visual cue. These findings point to a dissociation in the effect of explicit knowledge of object properties on grasp kinematics versus kinetics, thus suggesting independent anticipatory processes for grasping.

It has been shown that when subjects can predict object properties [e.g., weight or center of mass (CM)], fingertip forces are appropriately scaled before the object is lifted, i.e., before somatosensory feedback can be processed. However, it is not known whether subjects, in addition to these anticipatory force mechanisms, exploit the ability to choose where digits can be placed to facilitate object manipulation. We addressed this question by asking subjects to reach and grasp an object whose CM was changed to the left, center, or right of the object in either a predictable or unpredictable manner. The only task requirement was to minimize object roll during lift. We hypothesized that subjects would modulate contact points but only when object CM location could be predicted. As expected, object roll was significantly smaller in the predictable condition. This experimental condition was also associated with statistically distinct spatial distributions of contact points as a function of object CM location but primarily when large torques had to be counteracted, i.e., for right and left CM locations. In contrast, when subjects could not anticipate CM location, a “default” distribution of contact points was used, this being statistically indistinguishable from that adopted for the center CM location in the predictable condition. We conclude that choice of contact points is integrated with anticipatory force control mechanisms to facilitate object manipulation. These results demonstrate that planning of digit placement is an important component of grasp control.

This study assessed how hand shaping responds to a perturbation of object shape. In blocked trials (80% of total), subjects were instructed to reach, to grasp and lift a concave or a convex object. In perturbed trials (20% of total), a rotating device allowed for the rapid change from the concave to the convex object or vice versa. In this situation subjects grasped the last presented object. Flexion/extension at the metacarpal-phalangeal and proximal interphalangeal joints of all digits was measured by resistive sensors embedded in a glove. In the blocked condition we found that most joints of the fingers were modulated by the type of the to-be-grasped object during the reach. When object shape was perturbed, reach duration was longer and angular excursion of all fingers differed with respect to blocked trials. For the 'convex --concave' perturbation, a greater degree of finger extension was found than during the blocked 'concave' trials. In contrast, for the 'concave --convex' perturbation, fingers were more flexed than for the blocked 'convex' trials. The thumb reacted to the perturbation showing a similar pattern (i.e., over-flexion with respect to the blocked trials) regardless the 'direction' of the perturbation. The present results suggest that applying an object shape perturbation during a reach-to-grasp action determines a reorganization of all digits. This pattern is suggestive of a control strategy, which assigns to opposing digits different roles.

The ability to interact with other people hinges crucially on the possibility to anticipate how their actions would unfold. Recent evidence suggests that a similar skill may be grounded on the fact that we perform an action differently if different intentions lead it. Human observers can detect these differences and use them to predict the purpose leading the action. Although intention reading from movement observation is receiving a growing interest in research, the currently applied experimental paradigms have important limitations. Here, we describe a new approach to study intention understanding that takes advantage of robots, and especially of humanoid robots. We posit that this choice may overcome the drawbacks of previous methods, by guaranteeing the ideal trade-off between controllability and naturalness of the interactive scenario. Robots indeed can establish an interaction in a controlled manner, while sharing the same action space and guaranteeing contingent behaviors. To conclude, we discuss the advantages of this research strategy and the aspects to be taken in consideration when attempting to define which human (and robot) motion features allow for intention reading during social interactive tasks.

Recent advances in the field of cognitive neuroscience have revealed that direct gaze modulates activity in cortical and subcortical key regions of the ‘social brain network’, including the inferior frontal gyrus (IFG) and the anterior rostral medial prefrontal cortex (arMPFC). However, very little is known about how direct gaze is processed during live interaction with a real partner. Here, for the first time we used an experimental setup allowing the participant inside an MRI scanner to interact face-to-face with a partner located in the scanner room. Depending on condition, the participant and the partner were instructed either to look at each other in the eyes or to direct their gaze away from the other. As control conditions, participants gazed at their own eyes, reflected in a mirror, or gazed at a picture of the partner's eyes. Results revealed that direct gaze by the partner was associated with activity in areas involved in production and comprehension of language and action, including the IFG, the premotor cortex (PM), and the supplementary motor area (SMA). Activations in these areas were observed regardless of the participant's gaze behavior. In contrast, increased activity in arMPFC, an area involved in inference of other mental states during social interaction and communication, was only observed when the participant reciprocated the partner's direct gaze so as to establish mutual gaze. Psychophysiological interaction (PPI) analysis revealed effective connectivity between the IFG and the arMPFC during mutual gaze. This suggests that, within a larger network concerned with the processing of social gaze, mutual gaze with a real partner is established by an increased coupling between areas involved in the detection of communicative intentions, language, and social interaction.

The conceptual phase of design plays a crucial role about the overall performance of buildings. Early design choices have repercussions that are seldom controlled by designers in an effective way. More so, when quantities are involved in the decisions. This paper proposes a methodology for decision support during the conceptual design of buildings. The paper introduces a design knowledge representation framework and a computational mean for supporting the exploration of the design space through statistical inference. The proposed methodology is able to perform mixed inferences, combining symbolic and numerical computations.

We report a case of large pericardial effusion which has been managed with pericardiocentesis as the main presentation feature of a dramatic clinical picture, only retrospectively framed as referred to macrophage activation syndrome in a child with juvenile idiopathic arthritis at its onset. The risk of developing this rare and severe complication should be recognized in various pathological settings of childhood, above all in children displaying systemic signs of juvenile idiopathic arthritis.

Objective. To compare the antihypertensive effect of treatment with zofenopril vs candesartan by office and ambulatory blood pressure (BP). Design and methods. Following a 2‐week wash‐out from previous treatment, 236 grade I–II primary hypertensive patients were randomized double‐blind to 12 weeks treatment with zofenopril 30 mg or candesartan 8 mg od. After 4 weeks, treatment was doubled in responder non‐normalized (office systolic BP⩾140 mmHg and office diastolic BP reduction ⩾10 mmHg) or non‐responder patients (office systolic BP⩾140 mmHg and office diastolic BP reduction

Building Energy Management Systems consist of hardware and software components. The hardware set-up of BEMS is typically made up of a set of computers in charge of building control and sensoractuator networks. The software side of BEMS is usually made up of a number of functional layers that implement standard management functionalities. This paper will present an application of Model based Predictive Control (MPC) targeted to energy management of the “Passeig de Gracia” metro station in Barcelona. This approach uses the predictions of future building status, obtained by means of a set of Bayesian Networks, in order to determine the optimal control policies. First the predictive Bayesian Networks were developed through the following steps: structural learning based on a simulated dataset; improvement of the network’s topology through enhanced datasets derived from the previous one; final refinement and validation based on experimental data collected through a pervasive wireless monitoring network. Then those networks were integrated within a control framework, including control algorithms, a Dymola TM based virtual model of the station to simulate its evolvement and, on top of them, a user graphic interface to manage the system. The results about energy savings estimation determined by the application of model based predictive control to the station’s mechanical ventilation showed that as much as 35% can be saved on average.

Evidence exists that action observation activates the same cortical motor areas that are involved in the performance of the observed actions. An untested idea is whether subcortical structures such as the basal ganglia play a role in the coding of other people's actions. This study used kinematics to examine how Parkinson's disease patients react to the observation of an action which they were subsequently requested to perform. In each trial a model and an observer, which could be either a Parkinsonian patient or a neurologically healthy participant, were seated facing each other. The model was requested to grasp a stimulus (action condition), to perform a kicking action towards the stimulus (control-action condition), and to not perform any action (control condition). The task for the observer was always to grasp the stimulus after having watched the model performing her task. Results show that Parkinson's disease patients did show facilitation effects only when the model was a Parkinsonian patient. Whereas, neurologically healthy participants' movements were facilitated following the observation of either the Parkinsonian and the healthy model grasping the object. No facilitation effects were found for both the control and the control-action conditions. The fact that normal visuomotor priming takes place in PD patients when the observed action matches with what they can perform suggests that basal ganglia might not be necessary for it. However, damage to the basal ganglia might become relevant when such a match does not occur. In such circumstances, a damage to these structures might prevent the deployment of additional activity which might be necessary to influence cortical functions related to the representations of observed actions.

The purpose of this investigation was to evaluate the effectiveness of posterior pharyngeal and nasopharyngeal swabs in identifying and quantifying meningococcal carriage. Two swab samples were obtained from 564 healthy adolescents aged 15–19 years, the first taken from the posterior pharyngeal wall through the mouth and the second through the nose. Bacterial genomic DNA was extracted and screened for Neisseria meningitidis by means of two separate singleplex real-time polymerase chain reactions (real-time PCRs) in order to identify the CtrA and sodC genes. Subsequently, N. meningitidis-positive samples underwent a further singleplex real-time PCR in order to determine the N. meningitidis serogroup, and the DNA was quantified by means of standard curves. Thirty-seven subjects (6.6 %) were found to be carriers of N. meningitidis. The most frequently carried serogroup was serogroup B (15 cases, 40.5 %); serogroups A, Y, X, W135 and Z were found in, respectively, two (5.4 %), five (13.5 %), four (10.8 %), three (8.1 %) and one subject (2.7 %); the serogroup was not identified in seven cases. The detection of carrier status was significantly more frequent using posterior pharyngeal swabs (5.3 % vs. 2.1 %; p = 0.004), which also contained a significantly larger number of N. meningitidis genomic copies (4.91 ± 1.39 vs. 2.50 ± 0.8 log10 genomic copies/mL; p < 0.001). Posterior pharyngeal swabs seem to be better than nasopharyngeal swabs for detecting N. meningitidis carriage in large-scale epidemiological studies because they identify a significantly larger number of pathogen carriers and recover a significantly larger amount of bacterial DNA.

BackgroundHemophagocytic syndrome (HPS) is clinically defined as a combination of fever, liver dysfunction, coagulation abnormalities, pancytopenia, progressive macrophage proliferation throughout the reticuloendothelial system, and cytokine over-production, and may be primary or secondary to infectious, auto-immune, and tumoral diseases. The most consistent association is with viral infections but, as it is still debated whether any micro-organisms are involved in its pathogenesis, we critically appraised the literature concerning HPS and its relationship with infections.DiscussionInfection-dependent HPS has been widely observed, but there are no data concerning its incidence in children. A better understanding of the pathophysiology of HPS may clarify the interactions between the immune system and the variously implicated potential infectious agents. Epstein-Barr virus (EBV) infection has been prominently associated with HPS, with clonal proliferation and the hyperactivation of EBV-infected T cells. However, a number of other viral, bacterial, fungal, and parasitic infections have been reported in association with HPS. In the case of low-risk HPS, corticosteroids and/or intravenous immunoglobulin or cyclosporine A may be sufficient to control the biological process, but etoposide is recommended as a means of reversing infection-dependent lymphohistiocytic dysregulation in high-risk cases.SummaryHPS is a potential complication of various infections. A polymerase chain reaction search for infectious agents including EBV, cytomegalovirus andLeishmaniais recommended in clinical settings characterised by non-remitting fever, organomegaly, cytopenia and hyperferritinemia.

We applied phage display technology to DNA-protein interaction studies. A cDNA expression library displayed on the surface of bacteriophage lambda was generated from the highly differentiated MMH E14 murine hepatic cell line. Selection of this library using the promoter sequence of the liver-enriched transcription factor HNF1alpha gene as ligate identified DNA-binding domains specifically interacting with different regions of this regulatory sequence. One of the selected phage showed 100% identity to a DNA-binding domain shared by differentiation specific element-binding protein, vasoactive intestinal peptide receptor-repressor protein and replication factor C and was further investigated. Specific binding of the selected protein domain was confirmed in a phage-independent context. By combining ELISA and South-Western assays using the selected phage and a bacterially expressed glutathione-S-transferase protein fused to the encoded DNA-binding domain, an array of multiple adjacent DNA-binding sites sharing a common consensus motif was identified. The strategy described represents a powerful tool to identify proteins that bind to DNA regulatory elements. (C) 2002 Elsevier Science Ltd. All rights reserved.