Miracle-dz/UniFAR-FTUs huggingface dataset:
High handaxe symmetry at the beginning of the European Acheulian: The data from la Noira (France) in context

In the last few decades, new discoveries have pushed the beginning of the biface-rich European Acheulian from 500 thousand years (ka) ago back to at least 700 ka, and possibly to 1 million years (Ma) ago. It remains, however, unclear to date if handaxes arrived in Europe as a fully developed technology or if they evolved locally from core-and-flake industries. This issue is also linked with another long-standing debate on the existence and behavioral, cognitive, and social meaning of a possibly chronological trend for increased handaxe symmetry throughout the Lower Paleolithic. The newly discovered sites can provide a link between the much older Acheulian in Africa and the Levant and the well-known assemblages from the later European Acheulian, enabling a rigorous testing of these hypotheses using modern morphometric methods. Here we use the Continuous Symmetry Measure (CSM) method to quantify handaxe symmetry at la Noira, a newly excavated site in central France, which features two archaeological levels, respectively ca. 700 ka and 500 ka old. In order to provide a context for the new data, we use a large aggregate from the well-known 500 ka old site of Boxgrove, England. We show that handaxes from the oldest layer at la Noira, although on average less symmetric than both those from the younger layers at the same site and than those from Boxgrove, are nevertheless much more symmetric than other early Acheulian specimens evaluated using the CSM method. We also correlate trends in symmetry to degree of reduction, demonstrating that raw material availability and discard patterns may affect observed symmetry values. We conclude that it is likely that, by the time the Acheulian arrived in Europe, its makers were, from a cognitive and motor-control point of view, already capable of producing the symmetric variant of this technology.
Functional device models and model-Based diagnosis in adaptive design

Abstract We analyze the diagnosis task in the context of adaptive design and redesign of physical devices. We identify three types of diagnosis tasks that differ in the types of information they take as input: the design does not achieve a desired function of the device, the design results in an undesirable behavior, and a specific structural element in the design misbehaves. We describe a model-based approach for solving the diagnosis task in the context of adaptive design and redesign. This approach uses functional models that explicitly represent the device functions and use them to organize teleological and causal knowledge about the device. In particular, we describe a specific kind of functional model called structure—behavior—function (SBF) models in which the causal behaviors of the device are specified in terms of flow of substances through components. We illustrate the use of SBF models with three examples from Kritik2, a knowledge system that designs new devices by retrieving, diagnosing, and adapting old device designs.
The role of hydrolysates for allergy prevention--pro.

Allergen exposure in the first months of life is regarded as one main risk factor for the development of allergic diseases, in particular in infants with at least one-first-degree relative – parent or sibling – with a history of allergy (high-risk infant). The main early allergen contact for the infant derives from food allergens, mainly cow milk allergen. If for high-risk children breastfeeding is not sufficiently feasible in the first 4-6 months of life, a cow milk protein hydrolysate is the recommended supplement to avoid the early exposure to intact milk allergen (1–4). Hydrolysates (synonyma: cow milk protein hydrolysate formula, hypoallergenic formula, HA formula) are formulas processed by different technics to reduce the antigenicity of the intact milk protein. Dependent on the degree of hydrolysation and the protein source whey (W) or casein (C), they are classified in partial (pHF) or extensive (eHF) hydrolysates (5). eHFs, primarily intended for treatment of cow milk allergy (CMA), have later been used also for primary allergy prevention. pHFs were a priori made for allergy prevention only. eHFs are characterized by >90% of peptides with a molecular weight <1.5 kDawith almost no antigenicity, while pHFs have a higher residual antigenicity that is supposed to actively induce immune tolerance. From the available clinical data, however, there is nowadays reason to believe that themechanism of action of eHF is similarly active induction of immune tolerance rather than simply avoidance of antigen contact.
Measuring product semantic similarity by exploiting a manufacturing process ontology

The retrieval of manufacturing knowledge in companies is critical because product and process knowledge was not actually managed but only documented. Particularly, the identification of similarities between new and past products relied almost exclusively on the memory and the experience of people, and thus it is a time-consuming task. In this paper, a method to allow the automatic identification of past similar products is proposed, so that they can be used to speed up the design of manufacturing of the new product. The similarity is computed by using a semantic model in the form of ontology, which constitutes the hierarchical structure of concepts. A new similarity index is defined based on the portion of overlapping subgraph of concepts existing between two products. The different weight of each node is also considered because more descendants the node has, less specific its semantics information content is. The computation of the similarity measurement will allow the discovering of knowledge from stored data, thus supporting the engineers in searching for past products having similar characteristics with the new one. The potentiality of the proposed index is shown in a motivating example.
Migration of monocytes after intracerebral injection at entorhinal cortex lesion site

The lack of classical lymph vessels within brain tissue complicates immune surveillance of the CNS, and therefore, cellular emigration out of the CNS parenchyma requires alternate pathways. Whereas invasion of blood‐derived mononuclear cells and their transformation into ramified, microglia‐like cells in areas of axonal degeneration across an intact BBB have been demonstrated, it still remained unclear whether these cells reside permanently, undergo apoptosis, or leave the brain to present antigen in lymphoid organs. With the use of ECL of mice and injection of GFP‐expressing monocytes, we followed the appearance of injected cells in spleen and LNs and the migratory pathways in whole‐head histological sections. Monocytes migrated from the lesion site to deep CLNs, peaking in number at Day 7, but they were virtually absent in spleen and in superficial CLNs and inguinal LNs until Day 21 after lesion/injection. In whole‐head sections, GFP monocytes were found attached to the olfactory nerves and located within the nasal mucosa at 48 hpi. Thus, monocytes are capable of migrating from lesioned brain areas to deep CLNs and use the cribriform plate as an exit route.
Neuroinvasion of Fluorescein-Positive Monocytes in Acute Simian Immunodeficiency Virus Infection

ABSTRACT Monocytes and macrophages play a central role in the pathogenesis of human immunodeficiency virus (HIV)-associated dementia. They represent prominent targets for HIV infection and are thought to facilitate viral neuroinvasion and neuroinflammatory processes. However, many aspects regarding monocyte brain recruitment in HIV infection remain undefined. The nonhuman primate model of AIDS is uniquely suited for examination of the role of monocytes in the pathogenesis of AIDS-associated encephalitis. Nevertheless, an approach to monitor cell migration from peripheral blood into the central nervous system (CNS) in primates had been lacking. Here, upon autologous transfer of fluorescein dye-labeled leukocytes, we demonstrate the trafficking of dye-positive monocytes into the choroid plexus stromata and perivascular spaces in the cerebra of rhesus macaques acutely infected with simian immunodeficiency virus between days 12 and 14 postinfection (p.i.). Dye-positive cells that had migrated expressed the monocyte activation marker CD16 and the macrophage marker CD68. Monocyte neuroinvasion coincided with the presence of the virus in brain tissue and cerebrospinal fluid and with the induction of the proinflammatory mediators CXCL9/MIG and CCL2/MCP-1 in the CNS. Prior to neuroinfiltration, plasma viral load levels peaked on day 11 p.i. Furthermore, the numbers of peripheral blood monocytes rapidly increased between days 4 and 8 p.i. , and circulating monocytes exhibited increased functional capacity to produce CCL2/MCP-1. Our findings demonstrate acute monocyte brain infiltration in an animal model of AIDS. Such studies facilitate future examinations of the migratory profile of CNS-homing monocytes, the role of monocytes in virus import into the brain, and the disruption of blood-cerebrospinal fluid and blood-brain barrier functions in primates.
A Mutation-Classified, Parameter-Dynamic Immunological Algorithm for Global Optimization

Based on the artificial immune system, a new clonal selection algorithm is proposed to perform global optimization. The concept of classified mutation is defined and the dynamic adjustment methods of some evolution parameters are introduced. The proposed algorithm is applied to several benchmark problems, and its performance is compared with other approaches in the literature. The results indicate that the new algorithm is a significant advance in clonal selection and a viable alternative.
Cytokines in serum in relation to future non‐Hodgkin lymphoma risk: Evidence for associations by histologic subtype

Specific associations for lymphoma in the general population suggest that chronic immune dysfunction/dysregulation may be associated with the development of B‐cell non‐Hodgkin lymphoma (NHL). Furthermore, polymorphisms in several cytokine genes have been associated with increased lymphoma risk, most consistently with genes for TNF and IL10. To evaluate the hypothesis that prediagnostic circulating cytokine levels would be associated with increased B‐cell lymphoma risk, we conducted a nested case‐control study within the Women's Health Initiative Observational Study cohort involving 491 B‐cell NHL cases and 491 controls. Levels of eleven cytokines, including IL1β, IL2, IL4, IL5, IL6, IL10, IL12, IL13, TNF, IFNγ and GM‐CSF, were measured using a Luminex suspension bead‐based multiplexed array in prediagnostic serum samples collected a median of 6 years prior to the lymphoma diagnosis. We observed a modestly increased risk of all B‐cell NHL in women with increased levels of the cytokines TNF and IL10 (OR1.22, CI 1.07–1.38 and OR 1.09, CI 1.04–1.15, respectively, per doubling in the serum cytokine concentration) and this association showed some variation according to histologic subtype. The increased risk was strongest for those neoplasms diagnosed in close proximity to the blood draw for some histologic subtypes but not others, suggesting a component of reverse causation. Further study will be required to better understand how genetic polymorphisms in TNF and IL10 genes may interact with circulating cytokine levels and states of chronic immune dysfunction/stimulation to contribute to the risk of B‐cell NHL.
Fluorescent Probes as Tools to Assess the Receptor for the Urokinase-Type Plasminogen Activator on Tumor Cells

Flow cytofluorometric protocols (FACScan) are described for the rapid and quantitative real-time analysis of binding of FITC-pro-u-PA to cell surface receptors (u-PAR) on living, resting, and also on PMA-stimulated human monocytic U937 cells. Binding of pro-u-PA was visualized by CLSM. This fairly new technique is superior over conventional fluorescence microscopy and is an alternative to electron microscopic approaches. Both flow cytofluorometry and confocal laser scanning microscopy allow the analysis quantitatively and with high-sensitivity binding of FITC-pro-u-PA to single suspended or adherent cells. By CLSM u-PA/u-PAR were found to be located in heterogeneously distributed discrete patches at the cell surface on U937 and not inside the cell. This is in agreement with previous studies by Hansen et al, who applied radioiodinated u-PA and electron microscopy to locate u-PAR on microvilli of fixed U937 cells. By flow cytofluorometry, it was possible to quantify the time-dependent and temperature-dependent binding of FITC-pro-u-PA to living single U937. Apparent saturation of u-PAR was achieved at 5 nM FITC-pro-u-PA for both nonstimulated and PMA-stimulated U937 cells. Half saturation of u-PAR was also determined. Nonstimulated U937 was 0.7 nM, and PMA-stimulated U937 was 1.1 nM of FITC-pro-u-PA. This increase in half-saturation concentration in PMA-stimulated cells is paralleled by a steep increase in binding sites (3.6-fold). The use of fluoresceinated reference beads is recommended to verify changes in affinity and binding sites. Using CLSM or flow cytofluorometry, it is also possible to study the structure relationship of u-PA/u-PAR in the presence of competitive binding analogues or inhibitors. Fluorescence techniques will also permit the identification of u-PAR-positive cells in blood, ascitic fluid, or biopsies obtained from cancer patients.
Squamous cell carcinoma of head and neck in patients with well‐differentiated lymphocytic lymphoma

Seventy‐six cases of well‐differentiated lymphocytic lymphoma (WDLL) were reviewed for evidence of additional malignancies. Of these, 18 patients (24%) had one to three further tumors; one half (nine) had squamous cell carcinoma (SCC). The head and neck area was the primary site in all but one case of SCC. The carcinomas were frequently multiple, recurrent, and clinically aggressive. The tumors showed unusually poor differentiation histologically. Actinic keratosis and basal cell carcinomas were frequently associated with SCC. Fifty percent metastasized to cervical lymph nodes replaced by WDLL. Lymphadenopathy due to metastatic SCC may be mistaken for malignant lymphoma alone. In two of five patients (40%), death was directly attributable to SCC. As in renal transplant recipients, SCC of the head and neck in WDLL patients is a common cause of significant complications and mortality requiring aggressive management. Immunosuppression due to WDLL and/or to chemotherapy is likely an important predisposing factor in combination with sun exposure.
Redd Habitat Selection for Brook Trout in the Necktie River Bemidji, MN

The presence of quality suitable habitat is important for the success of naturally reproducing Brook Trout populations. Therefore, measuring redd habitat Brook Trout select for was the focus of this study. Brook Trout redds were observed during the spawning season of 2016. We identified a total of 18 redds in the Necktie River in late October and early November. Specific environmental variables associated with redd selection were measured: velocity, in-stream cover, canopy cover, bank overhang, river width, substrate type and size, temperature, and max-depth. The same environmental variables were measured for 30 randomly selected sites. Redds were distributed in riffles 85% of the time, and runs 15% of the time; random sites were distributed evenly throughout the system (43% in riffles and 57% in pools). Significant environmental variables associated with redds were substrates (P < 0.01), cover (P = 0.02), conductivity (P < 0.01), and dissolved oxygen (P < 0.01). All other variables showed no differences which indicated Brook Trout were not selecting for these variables. Although Brook Trout are more tolerant to ecosystem changes than other species of salmonids, they appear to be selecting for larger substrates. Therefore, future management should be focused on preserving or creating areas of suitable substrates to ensure maximum reproductive potential of the population.
HIGH-THROUGHPUT SYNTHESIS OF ENCODED HYDROGEL PARTICLES FOR BIOSENSING USING CONTACT FLOW LITHOGRAPHY

We report an automated cost-efficient method for the high-throughput fabrication of graphically encoded hydrogel microparticles for use in multiplexed biosensing. By combining automated flow lithography in a multichannel microfluidic device with contact lithography and a high capacity 1-inch UV source, we improve our production rate of chemically homogeneous particles by at least two orders of magnitude (> 10 6 100-micron sized particles per hour).
Author ' s personal copy Distinct and cooperative roles of mammalian Vg 1 homologs GDF 1 and GDF 3 during early embryonic development

Vg1, a member of the TGF-β superfamily of ligands, has been implicated in the induction of mesoderm, formation of primitive streak, and left– right patterning in Xenopus and chick embryos. In mice, GDF1 and GDF3 – two TGF-β superfamily ligands that share high sequence identity with Vg1 – have been shown to independently mimic distinct aspects of Vg1's functions. However, the extent to which the developmental processes controlled by GDF1 and GDF3 and the underlying signaling mechanisms are evolutionarily conserved remains unclear. Here we show that phylogenetic and genomic analyses indicate that Gdf1 is the true Vg1 ortholog in mammals. In addition, and similar to GDF1, we find that GDF3 signaling can be mediated by the type I receptor ALK4, type II receptors ActRIIA and ActRIIB, and the co-receptor Cripto to activate Smaddependent reporter genes. When expressed in heterologous cells, the native forms of either GDF1 or GDF3 were incapable of inducing downstream signaling. This could be circumvented by using chimeric constructs carrying heterologous prodomains, or by co-expression with the Furin proprotein convertase, indicating poor processing of the native GDF1 and GDF3 precursors. Unexpectedly, co-expression with Nodal – another TGF-β superfamily ligand involved in mesoderm formation – could also expose the activities of native GDF1 and GDF3, suggesting a potentially novel mode of cooperation between these ligands. Functional complementarity between GDF1 and GDF3 during embryonic development was investigated by analyzing genetic interactions between their corresponding genes. This analysis showed that Gdf1;Gdf3 compound mutants are more severely affected than either Gdf1 or Gdf3 single mutants, with defects in the formation of anterior visceral endoderm and mesoderm that recapitulate Vg1 loss of function, suggesting that GDF1 and GDF3 together represent the functional mammalian homologs of Vg1. © 2007 Elsevier Inc. All rights reserved.
Structural investigations of the active-site mutant Asn156Ala of outer membrane phospholipase A

Outer membrane phospholipase A (OMPLA) from Escherichia coliis an integral-membrane enzyme with a unique His–Ser–Asn catalytic triad. In serine proteases and serine esterases usually an Asp occurs in the catalytic triad; its role has been the subject of much debate. Here the role of the uncharged asparagine in the active site of OMPLA is investigated by structural characterization of the Asn156Ala mutant. Asparagine 156 is not involved in maintaining the overall active-site configuration and does not contribute significantly to the thermal stability of OMPLA. The active-site histidine retains an active conformation in the mutant notwithstanding the loss of the hydrogen bond to the asparagine side chain. Instead, stabilization of the correct tautomeric form of the histidine can account for the observed decrease in activity of the Asn156Ala mutant.
Protein ingestion preserves proteasome activity during intense aseptic inflammation and facilitates skeletal muscle recovery in humans

Abstract The ubiquitin–proteasome system (UPS) is the main cellular proteolytic system responsible for the degradation of normal and abnormal (e.g. oxidised) proteins. Under catabolic conditions characterised by chronic inflammation, the UPS is activated resulting in proteolysis, muscle wasting and impaired muscle function. Milk proteins provide sulphur-containing amino acid and have been proposed to affect muscle inflammation. However, the response of the UPS to aseptic inflammation and protein supplementation is largely unknown. The aim of this study was to investigate how milk protein supplementation affects UPS activity and skeletal muscle function under conditions of aseptic injury induced by intense, eccentric exercise. In a double-blind, cross-over, repeated measures design, eleven men received either placebo (PLA) or milk protein concentrate (PRO, 4×20 g on exercise day and 20 g/d for the following 8 days), following an acute bout of eccentric exercise (twenty sets of fifteen eccentric contractions at 30°/s) on an isokinetic dynamometer. In each trial, muscle biopsies were obtained from the vastus lateralis muscle at baseline, as well as at 2 and 8 d post exercise, whereas blood samples were collected before exercise and at 6 h, 1 d, 2 d and 8 d post exercise. Muscle strength and soreness were assessed before exercise, 6 h post exercise and then daily for 8 consecutive days. PRO preserved chymotrypsin-like activity and attenuated the decrease of strength, facilitating its recovery. PRO also prevented the increase of NF-κB phosphorylation and HSP70 expression throughout recovery. We conclude that milk PRO supplementation following exercise-induced muscle trauma preserves proteasome activity and attenuates strength decline during the pro-inflammatory phase.
Linear and Quadratic Solid-Shell Elements for Quasi-Static and Dynamic Simulations of Thin 3D Structures: Application to a Deep Drawing Process

A family of prismatic and hexahedral solid–shell (SHB) elements, with their linear and quadratic versions, is proposed in this work to model thin structures. The formulation of these SHB elements is extended to explicit dynamic analysis and large-strain anisotropic plasticity on the basis of a fully three-dimensional approach using an arbitrary number of integration points along the thickness direction. Several special treatments are applied to the SHB elements in order to avoid all locking phenomena and to guarantee the accuracy and efficiency of the simulations. These solid-shell elements have been implemented into ABAQUS standard/quasi-static and explicit/dynamic software packages. A number of static and dynamic benchmark problems, as well as a simulation of the deep drawing of a cylindrical cup, have been conducted to assess the performance of these SHB elements.
Drug drug interaction extraction from literature using a skeleton long short term memory neural network

Drug Drug Interactions (DDIs) can cause harmful effect. Two shared tasks, DDIExtraction 2011 and DDIExtraction 2013, have been held to promote the implementation and comparative assessment of natural language processing techniques in the field of the pharmacovigilance domain. However, few model can meanwhile achieve state-of-the-art performance on both tasks. A major reason is the lack of representation of DDI instance structure in common. Therefore, in this paper, we propose a novel method to make full use of the DDI structure based on deep learning, in which we grasp the skeleton structure of DDI instances by a skeleton long short term memory (skeleton-LSTM) network. The experimental results show that our method can achieve an F-score of 0.677 on DDIExtraction 2011 and an F-score of 0.714 on DDIExtraction 2013, both of which are state-of-the-art.