Miracle-dz/UniFAR-FTUs huggingface dataset:
Immunotherapy of cancer stem cells in solid tumors: initial findings and future prospective

Introduction: Conventional chemotherapies seemed to have reached a therapeutic plateau in the treatment of solid tumors and many metastatic diseases are still incurable. Events of chemo-resistance and relapses appear to be sustained by a subset of putative cancer stem cells (CSCs). New anticancer strategies need to face this new challenge exploring their efficacy against CSCs. Immunotherapy has raised enthusiasms in cancer therapy and its potential against CSCs is an intriguing field of research. Areas covered: In this work we reviewed the immunotherapy approaches directed against CSCs in solid tumors. We schematically divided adaptive immunotherapy strategies, mainly based on dendritic cell-vaccination, and strategies exploiting MHC-unrestricted effectors like natural killer cells, γδ T lymphocytes and cytokine-induced killer cells. Findings, strength and limitations of these models are discussed and compared highlighting their potential clinical relevance. Expert opinion: The important biologic role and clinical relevance of CSCs introduced a ‘noble target’ for immunotherapy and cancer treatments in general. Initial evidences suggest that CSCs may be susceptible to various types of immunotherapy attacks, overcoming their chemo-resistance. Investigation of important safety issues, based on shared features with ‘normal’ stem cells, along with intriguing synergisms with modulatory agents are open challenges for the next future and effective clinical translation.
The fascia of the limbs and back – a review

Although fasciae have long interested clinicians in a multitude of different clinical and paramedical disciplines, there have been few attempts to unite the ensuing diverse literature into a single review. The current article gives an anatomical perspective that extends from the gross to the molecular level. For expediency, it deals only with fascia in the limbs and back. Particular focus is directed towards deep fascia and thus consideration is given to structures such as the fascia lata, thoracolumbar fascia, plantar and palmar fascia, along with regional specializations of deep fascia such as retinacula and fibrous pulleys. However, equal emphasis is placed on general aspects of fascial structure and function, including its innervation and cellular composition. Among the many functions of fascia considered in detail are its ectoskeletal role (as a soft tissue skeleton for muscle attachments), its importance for creating osteofascial compartments for muscles, encouraging venous return in the lower limb, dissipating stress concentration at entheses and acting as a protective sheet for underlying structures. Emphasis is placed on recognizing the continuity of fascia between regions and appreciating its key role in coordinating muscular activity and acting as a body‐wide proprioceptive organ. Such considerations far outweigh the significance of viewing fascia in a regional context alone.
Regional Strengths of Bonding Agents to Cervical Sclerotic Root Dentin

The regional bond strengths of three current-generation bonding systems (All Bond 2, Scotchbond MultiPurpose, and Clearfil Liner Bond 2) were measured in natural wedge-shaped defects in the cervical area of extracted human teeth. A microtensile testing method was used to compare the strengths of resin bonds made to occlusal margins with those made to gingival margins. Controls consisted of normal teeth which had artificial wedge-shaped defects, of the same depth and dimension, created with a high-speed bur. The results indicated that there were no regional differences in bond strength, although bonds made to natural lesions were from 20 to 45% lower than those made to normal dentin in artificially created wedge-shaped defects, depending on the bonding agent. Scanning electron microscopy revealed that Clearfil Liner Bond 2 created the thinnest hybrid layers, which were difficult to measure in the natural lesions. The natural lesions contained sclerotic dentin, whereas the artificial lesions were composed of normal dentin. Although the bond strengths to sclerotic dentin were lower than those to normal dentin, the absolute values (ca. 16 to 17 MPa) were high relative to previous-generation bonding agents.
A large archosauriform tooth with multiple supernumerary carinae from the Upper Triassic of New Mexico (USA), with comments on carina development and anomalies in the Archosauria

Here we report a tooth of a large archosauriform from the Upper Triassic of New Mexico, USA that displays developmental anomalies of carina formation. This tooth has two supernumerary carinae, both on the lingual side of the tooth. Previously, carina anomalies of this sort were primarily known from theropod dinosaurs, but always from the labial surface. Integrating this specimen into a reassessment of the published accounts of carina anomalies in other fossil diapsids reveals that supernumerary carinae are more widespread throughout Archosauriformes than previously reported. Our interpretation of this developmental anomaly highlights the present lack of understanding of tooth development in archosaurs, particularly carina formation, and suggests that crown morphology development in archosauriforms may be constrained differently than it is in mammals. This developmental constraint may explain the differences observed between the complexity found in mammal and archosauriform cusp morphology.
The Routine Determination of the Endogenous Thrombin Potential, First Results in Different Forms of Hyper- and Hypocoagulability

Summary The area under the thrombin generation curve (the endogenous thrombin potential; ETP) has been proposed as a parameter for plasma-based hypercoagulability and to monitor anticoagulant treatment. We present an ETP assay for the routine laboratory using a centrifugal analyser. Throughput is 30 samples/h, within and between run imprecision is 4-5.6%. Suitable substrates were developed for the ranges of 10-500% and 2-100% of normal. Independent of tissue factor concentration (if >4 pM), the normal value of the extrinsic ETP is 384.8 ±51.7 nM.min. The intrinsic ETP, triggered by ellagic acid, is 414 ± 41 nM.min. The ETP is decreased to 15 and 35% of normal by oral anticoagulation (INR 2.5-4.0) and by heparin administration (APTT 1.5-2.5 X control). The ETP is increased in untreated subjects with congenital antithrombin deficiency and in women using oral contraceptives. In deep vein thrombosis (phlebographically confirmed), it is increased by 29.4% (extrinsic) and 53% (intrinsic). In (angiographically assessed) coronary artery disease the increase is by 10% and 17% respectively.
Standard Operating Procedure for Prospective Individualised Dosimetry for [131]I-rituximab Radioimmunotherapy of Non-Hodgkin's Lymphoma

Radioimmunotherapy (RIT) is an attractive therapy for non-Hodgkin's lymphoma (NHL) as it allows targeted tumor irradiation which provides a cytotoxic effect significantly greater than that of the immune-mediated effects of a non-radioactive, or ‘cold’, antibody alone. Anti-CD20 antibodies such as rituximab are ideal for RIT, as not only is it easily iodinated, but the CD20 antigen is found on more than 95% of B-cell NHL. A standard operating procedure (SOP) has been formulated for personalized prospective dosimetry for safe, effective outpatient 131I-rituximab RIT of NHL. Over five years, experience of treatment of outpatients with 131I-rituximab was analyzed with respect to critical organ radiation dose in patients and radiation exposure of their carers. This radiation safety methodology has been refined; and offers the potential for safe, practical application to outpatient 131I-rituximab RIT of lymphoma in general and in developing countries in particular. Given endorsement and sanction of this SOP by local regulatory authorities the personalized dosimetry paradigm will facilitate incorporation of RIT into the routine clinical practice of therapeutic nuclear oncology worldwide.
Identification of four conserved motifs among the RNA‐dependent polymerase encoding elements.

Four consensus sequences are conserved with the same linear arrangement in RNA‐dependent DNA polymerases encoded by retroid elements and in RNA‐dependent RNA polymerases encoded by plus‐, minus‐ and double‐strand RNA viruses. One of these motifs corresponds to the YGDD span previously described by Kamer and Argos (1984). These consensus sequences altogether lead to 4 strictly and 18 conservatively maintained amino acids embedded in a large domain of 120 to 210 amino acids. As judged from secondary structure predictions, each of the 4 motifs, which may cooperate to form a well‐ordered domain, places one invariant amino acid in or proximal to turn structures that may be crucial for their correct positioning in a catalytic process. We suggest that this domain may constitute a prerequisite ‘polymerase module’ implicated in template seating and polymerase activity. At the evolutionary level, the sequence similarities, gap distribution and distances between each motif strongly suggest that the ancestral polymerase module was encoded by an individual genetic element which was most closely related to the plus‐strand RNA viruses and the non‐viral retroposons. This polymerase module gene may have subsequently propagated in the viral kingdom by distinct gene set recombination events leading to the wide viral variety observed today.
A fully electronic DNA sensor with 128 positions and in-pixel A/D conversion

A 16 /spl times/ 8 sensor array chip for fully electronic DNA detection is presented. The sensor principle is based on an electrochemical redox cycling process. The chip is fabricated on the basis of an extended 0.5 /spl mu/m CMOS process. Each sensor site of the array chip contains a complete A/D converter with a dynamic range of five decades. The 3/spl sigma/-homogeneity of the electrical response of the sensor array is better than 6% (10/sup -11/ A to 10/sup -7/ A) and better than 20% (10/sup -12/ A to 10/sup -7/ A). Proper operation of the chip is demonstrated with electrochemical and biological experiments.
Activity, molecular forms, and cytochemistry of cholinesterases in developing rat diaphragm

Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were studied in the diaphragm of early postnatal rats, using radiometric determination of enzyme activities, velocity sedimentation for separation of molecular forms, and electron microscopic cytochemistry to localize enzymes. AChE activity did not change significantly during the first 2 months after birth. The level of 16 S AChE was high at early stages, but decreased to adult levels between days 19 and 32 after birth. In newborn and 8‐day‐old rats, 16 S and 13 S AChE were present in both endplate and extrajunctional muscle. In newborn muscle, BuChE activity was higher than AChE activity, but decreased 6‐fold by day 32. Newborn muscle contained 16 S, 10 S, and 4 S BuChE. The principal form throughout development was 4 S BuChE, but all forms diminished as total BuChE activity decreased with maturation. At early postnatal neuromuscular junctions, end product of both AChE and BuChE was present in the cleft, as well as in Schwann cells. More Schwann cells were present in early stages than in later stages, and this might account for part of the later decrease of BuChE activity measured biochemically.
Adhesion and Surface Issues in Cellulose and Nanocellulose

This paper provides a review of the scientific literature concerned with adhesion and surface properties of cellulose and nanocellulose. Cellulose is the most abundant chemical compound on earth and its natural affinity for self-adhesion has long been recognized. The ease of adhesion that occurs in cellulose has contributed to its use in paper and other fiber-based composite materials. Cellulose adhesion, which has received considerable attention over the past half century, occurs over a practical length scale ranging from the nanoscale to millimeters. Adhesion theories that have been examined in the bonding of cellulose fibers include: mechanical interlocking, adsorption or wetting theory, diffusion theory, and the theory of weak boundary layers. Cellulose fibers on the nanoscale are prepared in four different ways: (1) bacterial cellulose nanofibers, (2) cellulose nanofibers by electrospinning, (3) microfibrillated cellulose plant cell fibers and (4) nanorods or cellulose whiskers. Structure and properties of nanocellulose that are important include: morphology, crystalline structure, surface properties, chemical and physical properties, and properties in liquid suspension. Cellulosic nanofibers present a very high surface area which makes the adhesion properties the most important parameter to control for nanocomposite applications. In this paper, we will focus on discussion of the adhesion and surface characteristics of cellulose nanofibers that impact its properties and application in nanomaterials.
Influence of protein supplementation on site and extent of digestion, forage intake, and nutrient flow characteristics in steers consuming dormant bluestem-range forage.

Four multicannulated Holstein steers (initial BW 424 +/- 16 kg) were used in a 4 x 4 Latin square to determine the influence of protein supplementation on forage intake, site and extent of digestion, and nutrient flow in steers consuming dormant bluestem-range forage (2.3% CP). Treatments were 1) control, no supplement; 2) 1.8 kg of low-protein supplement, 12.8% CP (Low-CP); 3) 1.8 kg of moderate-protein supplement, 27.1% CP (Mod-CP); and 4) 2.7 kg of dehydrated alfalfa pellets, 17.5% CP (Dehy). The Dehy supplement was fed to provide the same amount of CP/d as Mod-CP, and all supplements provided similar amounts of ME/d. Forage DMI was increased (P less than .05) by feeding Mod-CP and Dehy. Ruminal OM digestibility was 39% greater (P less than .05) for the Mod-CP and Dehy supplementations than for the Low-CP supplementation and control. Ruminal CP digestibility was negative for all treatments, and control (-326%) was less (P less than .05) than supplemented treatments (average -27%). Total tract OM digestibility was greatest (P less than .10) for steers fed Mod-CP and least for control steers; Low-CP and Dehy steers were intermediate. Total tract NDF digestibility tended (P = .15) to be less with Low-CP than with Mod-CP and Dehy. Duodenal N flow was greater (P less than .05) with Mod-CP and Dehy than with Low-CP and control. In summary, supplementation with Mod-CP increased forage intake, digestion, and duodenal N flow compared with Low-CP or control; however, the response was similar when Mod-CP and Dehy supplements were fed to provide equivalent amounts of CP and ME daily.
Matched-unrelated-donor bone marrow transplantation for children with leukemia.

BACKGROUND AND PURPOSE This report describes the results of matched-unrelated-donor transplant for leukemia or myelodysplasia in the first 23 recipient children at a single medical center in Taiwan. METHODS Between August 1994 and February 2003, 23 consecutive children with leukemia or myelodysplasia underwent matched-unrelated-donor bone marrow transplantation (BMT). The preparative regimen consisted of fractionated total body irradiation and cyclophosphamide in 6 patients; busulfan in combination with etoposide and cyclophosphamide in 4 patients who received cranial irradiation before transplantation; and busulfan and cyclophosphamide in 13 patients. RESULTS Engraftment was achieved in 91.3% of cases. Acute graft-versus-host disease (GVHD) occurred in 18 of 21 patients who engrafted (85.7%). Event-free survival for all patients was 24.46 +/- 9.24%. The 12 children with standard-risk disease had better event-free survival than the 11 children with high-risk disease (46.88 +/- 15.03% vs 0%, p < or = 0.001). CONCLUSIONS The major obstacles to successful matched-unrelated-donor BMT are acute GVHD, relapse and infection. Early transplantation and patient selection, prophylactic and therapeutic maneuvers for GVHD, as well as appropriate donor selection and virus prophylaxis may improve the results.
DNA vaccines for targeting bacterial infections

DNA vaccination has been of great interest since its discovery in the 1990s due to its ability to elicit both humoral and cellular immune responses. DNA vaccines consist of a DNA plasmid containing a transgene that encodes the sequence of a target protein from a pathogen under the control of a eukaryotic promoter. This revolutionary technology has proven to be effective in animal models and four DNA vaccine products have recently been approved for veterinary use. Although few DNA vaccines against bacterial infections have been tested, the results are encouraging. Because of their versatility, safety and simplicity a wider range of organisms can be targeted by these vaccines, which shows their potential advantages to public health. This article describes the mechanism of action of DNA vaccines and their potential use for targeting bacterial infections. In addition, it provides an updated summary of the methods used to enhance immunogenicity from codon optimization and adjuvants to delivery techniques including electroporation and use of nanoparticles.
Mesocorticolimbic Dopamine Systems and Reward

Research during the past decade has generated a substantial body of evidence indicating that mesolimbic dopamine (DA) neurons are an important link in the neural circuitry of reward. Most of this evidence is based on the application of three procedures that are now commonly used to study reward mechanisms: intracranial selfstimulation, intravenous self-administration, and conditioned place preference. Some of the data that have been generated by each approach and that are relevant to the mesolimbic DA hypothesis of reward are reviewed below.
PARENTAL CARE AND MODE OF FERTILIZATION IN ECTOTHERMIC VERTEBRATES

Why is parental care performed by the female in some species and the male in others? Several answers have been proposed by theoretical studies (Trivers, 1972; Williams, 1975; Dawkins and Carlisle, 1976; Maynard Smith, 1977, 1978; Perrone and Zaret, 1979), but there have been few efforts to test alternative hypotheses against observed patterns of vertebrate parental behavior. The present paper attempts to (1) derive specific predictions from three alternative hypotheses which deal with mode of fertilization (internal versus external) and parental care evolution, and (2) test these predictions using a compilation of published data on occurrence and correlates of parental care in amphibians and teleost fishes. In a recent review of species with male parental care, Ridley (1978) concluded: "The data implicate the mode of fertilization as the most important variable determining which parent is selected to care. Parental care usually correlates with external fertilization. There exists two hypotheses to explain this: certainty of paternity and order of gamete release. It is likely that each is the final (evolutionary) cause in different phylogenetic lineages. " The "certainty of paternity" hypothesis stems from the assumption that a male is unlikely to care for offspring if those offspring are not his own genetic progeny (Alexander, 1974). Trivers (1972) hypothesized that reliability of paternity will be affected by mode of fertilization-since external fertilization is without oviposition delay, reliability of paternity may be greater than with internal fertilization.
Justificación y racionalidad desde la teoría dual del razonamiento

Un supuesto comun en la epistemologia es que hay un vinculo importante entre la nocion de justificacion y la racionalidad. Sin embargo, este vinculo es oscuro debido a que no existe consenso acerca de que es la racionalidad, ni tampoco existe una idea clara de la nocion de justificacion. El proposito de este trabajo es exponer como la teoria dual del razonamiento puede crear un �puente� entre la nocion de justificacion y la de racionalidad. Se argumentara que dicha teoria apoya, en cierta medida, una nocion externalista de la justificacion y una vision consecuencialista de la racionalidad.
Cripto-1 Activates Nodal- and ALK4-Dependent and -Independent Signaling Pathways in Mammary Epithelial Cells

ABSTRACT Cripto-1 (CR-1), an epidermal growth factor-CFC (EGF-CFC) family member, has a demonstrated role in embryogenesis and mammary gland development and is overexpressed in several human tumors. Recently, EGF-CFC proteins were implicated as essential signaling cofactors for Nodal, a transforming growth factor β family member whose expression has previously been defined as embryo specific. To identify a receptor for CR-1, a human brain cDNA phage display library was screened using CR-1 protein as bait. Phage inserts with identity to ALK4, a type I serine/threonine kinase receptor for Activin, were identified. CR-1 binds to cell surface ALK4 expressed on mammalian epithelial cells in fluorescence-activated cell sorter analysis, as well as by coimmunoprecipitation. Nodal is coexpressed with mouse Cr-1 in the mammary gland, and CR-1 can phosphorylate the transcription factor Smad-2 in EpH-4 mammary epithelial cells only in the presence of Nodal and ALK4. In contrast, CR-1 stimulation of mitogen-activated protein kinase and AKT in these cells is independent of Nodal and ALK4, suggesting that CR-1 may modulate different signaling pathways to mediate its different functional roles.
Ajuster l'analyse distributionnelle à un corpus spécialisé de petite taille

L'analyse distributionnelle sur des corpus specialises de taille modeste constitue un objectif applicatif important pour cette famille de methodes d'extraction des relations semantiques. Dans ce cadre, nous cherchons a optimiser le calcul distributionnel pour traiter un corpus de 2 millions de mots compose d'articles de la conference TALN. Notre expertise dans ce champ nous permet de constituer des donnees d'evaluation adaptees au corpus et a la tâche, et fait de cette configuration experimentale un lieu ideal pour observer precisement les mecanismes distributionnels a l'œuvre. Un parametrage precis du calcul distributionnel, depuis l'analyse syntaxique jusqu'aux mesures de proximite semantique, met en evidence la variete des resultats obtenus, particulierement selon les categories grammaticales des mots cibles, et permet de degager des combinaisons performantes en jouant sur le nombre, la nature et la qualite des contextes pris en compte dans le calcul.
An overview on Leishmania (Mundinia) enriettii: biology, immunopathology, LRV and extracellular vesicles during the host–parasite interaction

Abstract One of the Leishmania species known to be non-infective to humans is Leishmania (Mundinia) enriettii whose vertebrate host is the guinea pig Cavia porcellus. It is a good model for cutaneous leishmaniasis, chemotherapeutic and molecular studies. In the last years, an increased interest has emerged concerning the L. (Mundinia) subgenus after the finding of Leishmania (M.) macropodum in Australia and with the description of other new/putative species such as L. (M.) martiniquensis and ‘L. (M.) siamensis’. This review focused on histopathology, glycoconjugates and innate immunity. The presence of Leishmania RNA virus and shedding of extracellular vesicles by the parasite were also evaluated.
Estudio Argumental de las Construcciones Resultativas en la Gramática Española y su Equivalente al Inglés

El presente ensayo plantea reflexionar y analizar sobre algunas construcciones resultativas de la gramática española y su equivalente al inglés basado en un ámbito de interpretación. Se parte de la importancia de enfocarse en el estudio de las construcciones resultativas, comenzando de su definición general, demostrando su existencia en la lengua española y en la lengua inglesa, y se explicará por qué hay más productividad en la lengua inglesa que en la española, analizando los rasgos sintácticos, semánticos y pragmáticos, el significado global de la construcción y las clases semánticas de los verbos más recurrentes en las mismas. Finalmente, al igual que ocurre con los verbos calificados como realizaciones, existen sustantivos verbales que, dependiendo de la construcción en la que se realicen, denotan el desarrollo del evento y la obtención efectiva de su estado o lugar final.