Miracle-dz/UniFAR-FTUs huggingface dataset:
L‐CAM expression in lymph node and liver metastases of colorectal carcinomas

L‐CAM, also known as E‐cadherin, is a cell adhesion molecule expressed on the plasma membranes of epithelial cells at the intercellular interface. From in vitro gene transfection experiments the idea has been conceived that loss of L‐CAM expression might be related to the invasive capacity as well as metastatic potential of tumour cells. In several tumours a relation between the grade of differentiation and L‐CAM expression has been noticed: loss of differentiation appears to be associated with loss of L‐CAM immunoreactivity. Also, in lymph node metastases of poorly differentiated carcinomas loss of L‐CAM expression was demonstrated. In this study we describe L‐CAM expression in lymphogenous and haematogenous metastases of large bowel adenocarcinomas, using an indirect immunoperoxidase method with the monoclonal anti‐L‐CAM antibody 6F9. All the metastases studied—lymphogenous as well as haematogenous—demonstrated L‐CAM immunoreactivity in a pattern comparable to that of primary tumours. Intratumour heterogeneity in expression was noted, with normal intercellular, apical (non‐functional), and focally negative areas in the same tumour. The data indicate that primary tumours and their metastases do not differ strikingly in their pattern of L‐CAM expression. This would be consistent with transient rather than constitutive down‐regulation of L‐CAM in invasive and metastatic cancer cells.
Underground Incrementally Deployed Magneto-Inductive 3-D Positioning Network

Underground mines are characterized by a network of intersecting tunnels and sharp turns, an environment which is particularly challenging for radiofrequency based positioning systems due to extreme multipath, non-line-of-sight propagation, and poor anchor geometry. Such systems typically require a dense grid of devices to enable 3-D positioning. Moreover, the precise position of each anchor node needs to be precisely surveyed, a particularly challenging task in underground environments. Magneto-inductive (MI) positioning, which provides 3-D position and orientation from a single transmitter and penetrates thick layers of soil and rock without loss, is a more promising approach, but so far has only been investigated in simple point-to-point contexts. In this paper, we develop a novel MI positioning approach to cover an extended underground 3-D space with unknown geometry using a rapidly deployable anchor network. The key to our approach is that the position of only a single anchor needs to be accurately surveyed-the positions of all secondary anchors are determined using an iterative refinement process using measurements obtained from receivers within the network. This avoids the particularly challenging and time-intensive task in an underground environment of accurately surveying the positions of all of the transmitters. We also demonstrate how measurements obtained from multiple transmitters can be fused to improve localization accuracy. We validate the proposed approach in a man-made cave and show that, with a portable system that took 5 min to deploy, we were able to provide accurate through-the-earth location capability to nodes placed along a suite of tunnels.
Different patterns of apoptosis of HL‐60 cells induced by cycloheximide and camptothecin

Cells of the human promyelocytic HL‐60 line, when treated with a variety of antitumor agents in the presence of the protein synthesis inhibitor cycloheximide (CHX), or with CHX alone, rapidly undergo apoptosis (“active cell death”). It is presumed, therefore, that such cells are “primed” to apoptosis in that no new protein synthesis is required for induction of their death. We have studied apoptosis of HL‐60 cells triggered by the DNA topoisomerase I inhibitor camptothecin (CAM) in the absence and presence of CHX and apoptosis induced by CHX alone. Two different flcw cytometric methods were used, each allowing us to relate the apoptosis‐associated DNA degradation to the cell cycle position. Apoptosis induced by CAM was limited to S phase cells, e.g., at a CAM concentration of 0.15 μM, nearly 90% of the S phase cells underwent apoptosis after 4 h. In contrast, apoptosis triggered by CHX was indiscriminate, affecting all phases of the cycle: ∼40% of the cells from each phase the cycle underwent apoptosis at 5 μM CHX concentration. When CAM and CHX were added together, the pattern of apoptosis resembled that of cycloheximide alone, namely, cells in all phases of the cycle in similar proportion were affected. Thus, CHX, while itself inducing apoptosis of a fraction of cells, protected the S phase cells against apoptosis triggered by CAM. Because CHX (5 μM) did not significantly affect the rate of cell progression through S phase, the observed protective effect was most likely directly related to inhibition of protein synthesis, rather than to its possible indirect effect on DNA replication. Furthermore, whereas apoptosis (DNA degradation) triggered by CAM was prevented by the serine protease inhibitor N‐tosyl‐L‐lysylchloromethyl ketone (TLCK), this process was actually potentiated by this inhibitor when induced by CHX. The present data indicate differences in mechanism of apoptosis triggered by CAM (and perhaps other antitumor drugs) as compared with CHX. Apoptosis caused by CHX may be unique in that it may not involve new protein synthesis. These data are compatible with the assumption that the loss of a hypothetical, rapidly turning over suppressor of apoptosis may be the trigger of apoptosis of HL‐60 cells treated with CHX, whereas de novo protein synthesis is required when apoptosis is triggered by other agents. © 1993 Wiley‐Liss, Inc.
Endothelial function in patients with chronic obstructive pulmonary disease: a systematic review of studies using flow mediated dilatation

ABSTRACT Background: Cardiovascular disease is an important cause of morbidity and mortality in chronic obstructive pulmonary disease (COPD). Endothelial function may be involved in the pathogenesis of cardiovascular disease. In contrast to the attention given to pulmonary endothelial dysfunction, little is known about peripheral vascular changes in COPD. Therefore, we reviewed the literature on peripheral endothelial function in COPD. Methods: Databases were screened for studies using ultrasound-based flow-mediated dilation (FMD), the reference method for assessing peripheral endothelial function, in stable COPD patients. Pooled effect sizes were calculated using random effects model. Results: 17 studies were identified, with a total of 1228 participants (724 COPD patients; 504 controls). Pooled analysis demonstrated an impaired endothelial-dependent FMD (−3.22%; 95% confidence interval (CI) −4.74 to −1.69; p < 0.001; I2 = 96%) and endothelial-independent FMD (−2.86%; 95%CI −5.63 to −0.09; p = 0.04; I2 = 83%) in COPD patients when compared with smoking and non-smoking controls. Conclusion: This review provides evidence for impaired peripheral endothelial function in COPD. Since impaired endothelial function may contribute to cardiovascular morbidity, a more comprehensive cardiovascular phenotyping is considered important in COPD to address cardiovascular risk. A high frequency of cardiovascular comorbidity is observed in COPD patients, and therefore well-controlled, larger studies that investigate endothelial function in COPD patients are recommended.
The effect of platelet-rich plasma on the coronally advanced flap root coverage procedure: a pilot human trial.

BACKGROUND Coronally advanced flap (CAF) has been shown to effectively treat gingival recession. Platelet-rich plasma (PRP), containing autologous growth factors, has been shown to promote soft tissue healing. Therefore, the purpose of this study was to evaluate the effects of PRP in combination with CAF. METHODS Twenty-four systemically healthy patients participated in this study. A single Miller's Class I buccal recession defect per patient was treated. These patients were randomly assigned into CAF or PRP + CAF groups. Clinical parameters included recession depth (RD), recession width (RW), gingival thickness (GT), width of keratinized tissue (WKT), clinical attachment level (CAL), probing depth (PD), plaque index (PI), wound healing index (WHI), and gingival index (GI). PRP was prepared from whole blood drawn prior to surgery and applied to root surfaces. Patients were followed at 2, 4, 12, and 24 weeks post-surgery. RESULTS Twenty-three patients completed the study. The RD at 24 weeks was significantly reduced from 2.9 +/- 0.5 to 0.5 +/- 0.6 mm in the CAF group (P < 0.05) and from 2.8 +/- 0.2 to 0.5 +/- 0.7 mm in the PRP + CAF group (P < 0.05). The mean root coverage was 83.5% +/- 21.8% in the CAF group and 81.0% +/- 28.7% in the CAF + PRP group (P > 0.05). Fourteen out of 23 patients (60.9%) experienced 100% root coverage at the 24-week postoperative follow-up. CONCLUSION Based on the results of this pilot study, the application of PRP in CAF root coverage procedure provides no clinically measurable enhancements on the final therapeutic outcomes of CAF in Miller's Class I recession defects.
Degradation of Human PDZ-Proteins by Human Alphapapillomaviruses Represents an Evolutionary Adaptation to a Novel Cellular Niche

In order to complete their life cycle, papillomaviruses have evolved to manipulate a plethora of cellular pathways. The products of the human Alphapapillomavirus E6 proteins specifically interact with and target PDZ containing proteins for degradation. This viral phenotype has been suggested to play a role in viral oncogenesis. To analyze the association of HPV E6 mediated PDZ-protein degradation with cervical oncogenesis, a high-throughput cell culture assay was developed. Degradation of an epitope tagged human MAGI1 isoform was visualized by immunoblot. The correlation between HPV E6-induced degradation of hMAGI1 and epidemiologically determined HPV oncogenicity was evaluated using a Bayesian approach within a phylogenetic context. All tested oncogenic types degraded the PDZ-containing protein hMAGI1d; however, E6 proteins isolated from several related albeit non-oncogenic viral types were equally efficient at degrading hMAGI1. The relationship between both traits (oncogenicity and PDZ degradation potential) is best explained by a model in which the potential to degrade PDZ proteins was acquired prior to the oncogenic phenotype. This analysis provides evidence that the ancestor of both oncogenic and non-oncogenic HPVs acquired the potential to degrade human PDZ-containing proteins. This suggests that HPV E6 directed degradation of PDZ-proteins represents an ancient ecological niche adaptation. Phylogenetic modeling indicates that this phenotype is not specifically correlated with oncogenic risk, but may act as an enabling phenotype. The role of PDZ protein degradation in HPV fitness and oncogenesis needs to be interpreted in the context of Alphapapillomavirus evolution.
Spatial econometrics principles and challenges in Jean Paelinck's research

Abstract This special issue contains a selection of many excellent papers and posters presented at the Sixth ‘Jean Paelinck’ Seminar of Spatial Econometrics, which was held at the Universidad Autónoma de Madrid (UAM) in October, 2013. The collection of papers addresses some of the major concerns and progression lines proposed by professor Paelinck along his academic life for spatial econometrics: the treatment of spatial data and the need to specify and estimate appropriate econometric models in the realm of regional and urban science. The first two papers in this issue present two methods to detect spatial clusters (Rodero-Cosano, Salinas-Pérez, García-Alonso and Salvador-Carulla) and concentrations (Thomas-Agnan and Bonneu) using homogeneous micro-data and individual observations, respectively, to adequately deal with the Modifiable Areal Unit Problem. The following three articles focus on the specification of spatial effects—spatial autocorrelation and spatial heterogeneity—in more complex situations. Le Gallo and Chasco propose a non-parametric approach to deal with spatial effects when the model's parametric structure is unknown, as it is the case in hedonic models with large databases. Ezcurra and Ríos derive a spatial Durbin panel data model from theory in order to model the spatio-temporal relationship between output volatility and regional growth. Finally, Díaz-Lanchas, Gallego, Llano and De la Mata take into account spatial complexity in trade flows introducing spatial dependence in a gravity model.
Thy1+ Sca1+ innate lymphoid cells infiltrate the CNS during autoimmune inflammation, but do not contribute to disease development

IL‐23 is absolutely crucial for the development of T‐cell driven autoimmune disease in mice. Even though IL‐23 is widely held to be involved in the stabilization of IL‐17‐secreting T cells, naïve T cells lack the IL‐23 receptor. Thus, the primary cellular target of IL‐23 in the context of autoimmunity is a subject of some debate. Innate lymphoid cells (ILCs) are a recently discovered family of lymphocytes being involved in early host defense, particularly at mucosal epithelial surfaces. Given the fact that RORγt‐dependent ILCs (group 3 ILCs) constitutively express the IL‐23‐receptor, and that they have been implicated in intestinal autoimmunity, we hypothesized that ILCs could contribute to the early development of autoimmune neuroinflammation. Through systematic analysis, we detected a sizable population of Thy1+ Sca1+ ILCs in the inflamed CNS tissue. CNS‐infiltrating ILCs were characterized by expression of the IL‐7‐receptor and production of proinflammatory IL‐17 and IFN‐γ. Furthermore, genetic fate‐mapping revealed their dependence on the transcription factor RORγt. However, upon specific in vivo ablation of this cell population, we found that they do not influence the course of the disease.
A New Context‐Based Approach to Assess Marine Mammal Behavioral Responses to Anthropogenic Sounds

Abstract: Acute effects of anthropogenic sounds on marine mammals, such as from military sonars, energy development, and offshore construction, have received considerable international attention from scientists, regulators, and industry. Moreover, there has been increasing recognition and concern about the potential chronic effects of human activities (e.g., shipping). It has been demonstrated that increases in human activity and background noise can alter habitats of marine animals and potentially mask communications for species that rely on sound to mate, feed, avoid predators, and navigate. Without exception, regulatory agencies required to assess and manage the effects of noise on marine mammals have addressed only the acute effects of noise on hearing and behavior. Furthermore, they have relied on a single exposure metric to assess acute effects: the absolute sound level received by the animal. There is compelling evidence that factors other than received sound level, including the activity state of animals exposed to different sounds, the nature and novelty of a sound, and spatial relations between sound source and receiving animals (i.e., the exposure context) strongly affect the probability of a behavioral response. A more comprehensive assessment method is needed that accounts for the fact that multiple contextual factors can affect how animals respond to both acute and chronic noise. We propose a three‐part approach. The first includes measurement and evaluation of context‐based behavioral responses of marine mammals exposed to various sounds. The second includes new assessment metrics that emphasize relative sound levels (i.e., ratio of signal to background noise and level above hearing threshold). The third considers the effects of chronic and acute noise exposure. All three aspects of sound exposure (context, relative sound level, and chronic noise) mediate behavioral response, and we suggest they be integrated into ecosystem‐level management and the spatial planning of human offshore activities.
An Anatomically Based Finite Element Model of the Lower Limbs in the Seated Posture

In this study an anatomically accurate 3D Finite Element (FE) model of the lower limbs was developed from axial cryosection images of the Visible Man (VM). The relative position of the lower limbs of a subject in standing and sitting positions was acquired with a laser scanner. A subset of these data points were used as control points in a novel application of the Host Mesh Fitting (HMF) technique, where the generic model geometry was morphed to subject data in the standing position, and then this subject-specific model was articulated to the seated posture. The gluteus maximus muscle and a portion of the skin mesh of the customised model were selected to provide a framework with which to examine the mechanics of sitting. Passive material properties were taken from the literature and were implemented in two two-parameter Mooney-Rivlin models to assess the response of the anatomical models to applied forces and pressures. The average deformation of the skin mesh was 0.77plusmn1. 525 mm which resulted in a maximum von Mises stress of 3.98 kPa. The average deformation of the gluteus maximus mesh was 2.69 plusmn 0.6 mm which produced a maximum von Mises stress of 43 kPa. The results of the von Mises stress distribution support the theory that the highest stress occurs in the region immediately beneath the ischial tuberosities. The results of this research confirm previous conclusions reached using geometrically less complex models and the application of customisation to non linear mechanics provides a novel avenue to quantitatively assess office chair design and to analyse the mechanics of sitting.
A comprehensive review of the nasal microbiome in chronic rhinosinusitis (CRS)

Chronic rhinosinusitis (CRS) has been known as a disease with strong infectious and inflammatory components for decades. The recent advancement in methods identifying microbes has helped implicate the airway microbiome in inflammatory respiratory diseases such as asthma and COPD. Such studies support a role of resident microbes in both health and disease of host tissue, especially in the case of inflammatory mucosal diseases. Identifying interactive events between microbes and elements of the immune system can help us to uncover the pathogenic mechanisms underlying CRS. Here we provide a review of the findings on the complex upper respiratory microbiome in CRS in comparison with healthy controls. Furthermore, we have reviewed the defects and alterations of the host immune system that interact with microbes and could be associated with dysbiosis in CRS.
A genetically engineered ovarian cancer mouse model based on fallopian tube transformation mimics human high‐grade serous carcinoma development

Recent evidence suggests that ovarian high‐grade serous carcinoma (HGSC) originates from the epithelium of the fallopian tube. However, most mouse models are based on the previous prevailing view that ovarian cancer develops from the transformation of the ovarian surface epithelium. Here, we report the extensive histological and molecular characterization of the mogp–TAg transgenic mouse, which expresses the SV40 large T‐antigen (TAg) under the control of the mouse müllerian‐specific Ovgp‐1 promoter. Histological analysis of the fallopian tubes of mogp–TAg mice identified a variety of neoplastic lesions analogous to those described as precursors to ovarian HGSC. We identified areas of normal‐appearing p53‐positive epithelium that are similar to ‘p53 signatures’ in the human fallopian tube. More advanced proliferative lesions with nuclear atypia and epithelial stratification were also identified that were morphologically and immunohistochemically reminiscent of human serous tubal intraepithelial carcinoma (STIC), a potential precursor of ovarian HGSC. Beside these non‐invasive precursor lesions, we also identified invasive adenocarcinoma in the ovaries of 56% of the mice. Microarray analysis revealed several genes differentially expressed between the fallopian tube of mogp–TAg and wild‐type (WT) C57BL/6. One of these genes, Top2a, which encodes topoisomerase IIα, was shown by immunohistochemistry to be concurrently expressed with elevated p53 and was specifically elevated in mouse STICs but not in the surrounding tissues. TOP2A protein was also found elevated in human STICs, low‐grade and high‐grade serous carcinoma. The mouse model reported here displays a progression from normal tubal epithelium to invasive HGSC in the ovary, and therefore closely simulates the current emerging model of human ovarian HGSC pathogenesis. This mouse therefore has the potential to be a very useful new model for elucidating the mechanisms of serous ovarian tumourigenesis, as well as for developing novel approaches for the prevention, diagnosis and therapy of this disease. Published 2014. This article has been contributed to by US Government employees and their work is in the public domain in the USA.
[Composition and structure of the neuronal membrane: molecular basis of its physiology and pathology].

INTRODUCTION AND OBJECTIVE Neurons besides its ability to selectively detect signals from their surrounding, are able to integrate then in time and space when transmitting their message to other cells. This exceptional ability of the neuron is mainly due to the composition and characteristics of its plasma membrane. In this review, starting with a description of the general principles of cell membrane organization, on which the nerve cell membrane structure is based, we describe the structures and functions which are unique and peculiar to the neuronal membrane and its implications in pathological processes. DEVELOPMENT This review article starts with a description of the lipids forming the neuronal membrane, and the forces which maintain their cohesion to form the basic structure of the membrane. We describe some of the intrinsic biophysical properties of biological bilayers, and also to make special mention of the neuronal membrane proteins, both peripheral and integral proteins which are, finally, responsible for specificity and functional differentiation of the neurons. CONCLUSIONS Now a days, it is becoming clear that the knowledge of the neuronal membrane at the molecular level, specially the proteins involved in neuronal activity, is basic to understand neuronal physiology and pathology. Many disorders of the nervous system have their origins in defective synthesis or incorrect functioning of a particular protein in the neuronal membrane.