Miracle-dz/UniFAR-FTUs huggingface dataset:
ROLE OF ICAM-1-MEDIATED ENDOCYTOSIS IN ENDOTHELIAL FUNCTION AND IMPLICATIONS FOR CARRIER-ASSISTED DRUG DELIVERY

Title of Document: ROLE OF ICAM-1-MEDIATED ENDOCYTOSIS IN ENDOTHELIAL FUNCTION AND IMPLICATIONS FOR CARRIER-ASSISTED DRUG DELIVERY. Daniel Serrano, Doctor of Philosophy 2014 Directed By: Associate Professor Silvia Muro Fischell Department of Bioengineering, Clark School of Engineering, and Institute for Bioscience and Biotechnology Research Intercellular adhesion molecule 1 (ICAM-1) is a transmembrane protein found on the surface of vascular endothelial cells (ECs). Its expression is upregulated at inflammatory sites, allowing for targeted delivery of therapeutics using ICAM-1-binding drug carriers. Engagement of multiple copies of ICAM-1 by these drug carriers induces cell adhesion molecule (CAM)mediated endocytosis, which results in trafficking of carriers to lysosomes and across ECs. Knowledge about the regulation behind CAM-mediated endocytosis can help improve drug delivery, but questions remain about these regulatory mechanisms. Furthermore, little is known about the natural function of this endocytic pathway. To address these gaps in knowledge, we focused on two natural binding partners of ICAM-1 that potentially elicit CAM-mediated endocytosis: leukocytes (which bind ICAM-1 via β2 integrins) and fibrin polymers (a main component of blood clots which binds ICAM-1 via the γ3 sequence). First, inspired by properties of these natural binding partners, we varied the size and targeting moiety of model drug carriers to determine how these parameters affect CAM-mediated endocytosis. Increasing ICAM-1targeted carrier size slowed carrier uptake kinetics, reduced carrier trafficking to lysosomes, and increased carrier transport across ECs. Changing targeting moieties from antibodies to peptides decreased particle binding and uptake, lowered trafficking to lysosomes, and increased transport across ECs. Second, using cell culture models of leukocyte/EC interactions, inhibiting regulatory elements of the CAM-mediated pathway disrupted leukocyte sampling, a process crucial to leukocyte crossing of endothelial layers (transmigration). This inhibition also decreased leukocyte transmigration across ECs, specifically through the transcellular route, which occurs through a single EC without disassembly of cell-cell junctions. Third, fibrin meshes, which mimic blood clot fragments/remnants, bound to ECs at ICAM-1-enriched sites and were internalized by the endothelium. Inhibiting the CAM-mediated pathway disrupted this uptake. Following endocytosis, fibrin meshes trafficked to lysosomes where they were degraded. In mouse models, CAM-mediated endocytosis of fibrin meshes appeared to remove fibrin remnants at the endothelial surface, preventing re-initiation of the coagulation cascade. Overall, these results support a link between CAM-mediated endocytosis and leukocyte transmigration as well as uptake of fibrin materials by ECs. Furthermore, these results will guide the future design of ICAM-1-targeted carrier-assisted therapies. ROLE OF ICAM-1-MEDIATED ENDOCYTOSIS IN ENDOTHELIAL FUNCTION AND IMPLICATIONS FOR CARRIER-ASSISTED DRUG DELIVERY.
Earnings Management around Founder CEO Re-appointments and Successions in Family Firms

This paper studies CEO re-appointment and succession events in listed family firms with an incumbent family CEO in France, Germany and the UK over 2001-2016. The paper explores whether family firms with a founder CEO are more likely to engage in earnings management pre-event than other family firms and non-family firms. Compared to non-family firms, family firms practice less upward earnings management. Nevertheless, we find evidence of pre-event upward earnings management for firms that re-appoint their founder CEO, but no such earnings management for other family firms. Finally, we also show that the new CEOs in non-family firms engage in upward earnings management after their appointment.
Southern Appalachian Peatlands Sustain Unique Assemblages of Archaea

Numerous aspects of three peatlands (Pineola Bog, NC, Sugar Mountain Bog, NC, and Tater Hill Bog, NC) located along the Southern Appalachian highlands of western North Carolina were analyzed to elucidate the impact on future climatic warming events via the release of the greenhouse gas methane. Quantitative analyses demonstrated a methanogenic community comprising roughly 50% of the Archaeal. A hydrogenotrophic Methanobacterium sp. was enriched for from Pineola Bog using culture-based techniques, corroborating molecular data and indicating the presence of Methanobacteriales species (0.4%) in this peatland. In addition to the methanogenic population, many non-methanogenic species were also found among the peatlands both from DNA and cDNA analyses. Members of the deep-branching Euryarchaeota, represented 5-18% of the sequences retrieved from each of the three sites. Crenarchaeota numbers were found to significantly contribute to the overall Archaeal community across sites. Methane emission studies revealed the peak methane production to be just below (0-25 cm) the surface of the water table in each site, as was expected. Nutrient analysis of the study sites indicated a strong signature from the underlying bedrock of the area as concentrations of Fe, Al, and Na were at the high end of normal compared to other peatlands globally.
Applied Practice and Possible Leverage Points for Information Technology Support for Patient Screening in Clinical Trials: Qualitative Study

Background Clinical trials are one of the most challenging and meaningful designs in medical research. One essential step before starting a clinical trial is screening, that is, to identify patients who fulfill the inclusion criteria and do not fulfill the exclusion criteria. The screening step for clinical trials might be supported by modern information technology (IT). Objective This explorative study aimed (1) to obtain insights into which tools for feasibility estimations and patient screening are actually used in clinical routine and (2) to determine which method and type of IT support could benefit clinical staff. Methods Semistandardized interviews were conducted in 5 wards (cardiology, gynecology, gastroenterology, nephrology, and palliative care) in a German university hospital. Of the 5 interviewees, 4 were directly involved in patient screening. Three of them were clinicians, 1 was a study nurse, and 1 was a research assistant. Results The existing state of study feasibility estimation and the screening procedure were dominated by human communication and estimations from memory, although there were many possibilities for IT support. Success mostly depended on the experience and personal motivation of the clinical staff. Electronic support has been used but with little importance so far. Searches in ward-specific patient registers (databases) and searches in clinical information systems were reported. Furthermore, free-text searches in medical reports were mentioned. For potential future applications, a preference for either proactive or passive systems was not expressed. Most of the interviewees saw the potential for the improvement of the actual systems, but they were also largely satisfied with the outcomes of the current approach. Most of the interviewees were interested in learning more about the various ways in which IT could support and relieve them in their clinical routine. Conclusions Overall, IT support currently plays a minor role in the screening step for clinical trials. The lack of IT usage and the estimations made from memory reported by all the participants might constrain cognitive resources, which might distract from clinical routine. We conclude that electronic support for the screening step for clinical trials is still a challenge and that education of the staff about the possibilities for electronic support in clinical trials is necessary.
Macrophage chitin binding proteins in phagocytosis and M1 activation in response to chitin microparticles (172.27)

Unlike soluble or non-phagocytosable 40 - 100 µm chitin, chitin microparticles (1 - 10 μm, CMP) induce MAPK activation within 20 min in a manner dependent on TLR2, phagocytosis and a cellular cholesterol-mediated mechanism, followed by a typical expression of M1 phenotypes. Based on the previous studies, we hypothesized that trans-membrane signal through surface TLR2 ligation is insufficient and additional chitin binding proteins (CBP) involved in the early CMP phagocytosis are obligatory for M1 activation; CBP are distinct between M1/M2 macrophages (MΦ). Peritoneal M1, M2 and control MΦ were isolated from mice 1 - 2 days after ip administration of CMP, 40 - 100 µm chitin, and saline, respectively. These MΦ were cultured with CMP; CMP with CBP were isolated shortly after phagocytosis, stained by specific antibodies and analyzed by FACS. Several CBP on CMP, including TLR2, CD206, CD62L, CHI3L1, and LAMP-1, exhibited distinct patterns between M1/M2 activations. For example, TLR2, fully engaged at the early phagocytosis, was increased in M1 and reduced in M2 relative to unstimulated MΦ. Our results suggest that, although exact mechanisms of CBP-mediated M1 activation still remain to be elucidated, the profiles of selected CBP that bind to CMP during phagocytosis are associated with the polarization of MΦ. These profiles offer a potential tool as diagnostic/prognostic biomarkers to monitor chronic inflammatory diseases and the efficacy of immunotherapy.
Lung and Systemic Inflammation in COPD

Nuclear factor-κB (NF-κB) is a nuclear transcription factor first recognized in 1986 by Sen and Baltimore. Its name derives from the fact that it was first diagnosed in the nuclei of B cells [13] bound to an enhancer element of the immunoglobulin kappa light chain gene [4]. At that time, NF-κB was primarily thought to be a B-cell–specific transcription factor, but it was afterward found to be present in every cell type [5]. NF-κB has been implicated in the regulation of host inflammatory [6-8] and immune responses [9-11], cell adhesion [12], developmental signals [13], cell proliferation, differentiation [14, 15] and in defending cells from apoptosis [16, 17]. In addition, it plays important roles in cellular growth properties by encoding cytokines, chemokines and receptors required for neutrophil adhesion and migration, thus increasing the expression of specific cellular genes [18].
Potential role of organic matters and phosphate-solubilizing bacteria on growth of mungbean (Vigna radiata) and their response to management of phytonematodes

An experiment was conducted during 2007–09 to eplore addition of organic matters and phosphate-salubilizing bacteria (PSB) to soil as an alternative means of organic management of nematodes under field condition at Aligarh, Uttar Pradesh. Organic matters in the form of oilseed cakes of neem (Azadirachta indica Adr. Juss.), castor (Ricinus communis L.), groundnut (Arachis hypogaea L.), linseed (Linum usitatissimum) and sunflower (Helianthus annuus L.) were found to be highly efficacious in reducing the multiplication of plant-parasitic nematodes Meloidogyne incognita (Kofold & White) Chitwood, Rotylenchulus reniformis Limnford & Oliveira, Tylenchorhynchus brassicae, etc. The plant growth parameters such as plant weight, pollen fertility (%), pods/plant, root-nodulation and chlorophyll content of mungbean [Vigna radiata (L.) R. Wilczek] increased significantly. The multiplication rate of phyto-nematodes and number of root- galls caused by M. incognita greatly affected in the presence of Pseudomonas fluorescens (Trevisan) Migula as compared to its absence. Damage caused by the nematodes was further reduced when Pseudomonas fluorescens was added along with the oilseed cakes. Neem-cake was found most effective in combination with Pseudomonas fluorescens.
Water deficit-related expressed sequence tags (ESTS) in the sugarcane (Saccharum spp.) leaf roll.

WATER STRESS is one of the most common environmental stresses which affect plant productivity and their geographic distribution. Plants have mechanisms for water stress adaptation that might be characterised by the accumulation of specific mRNAs as the result of specific gene activation. In this work, expressed sequence tags (ESTs) from sugarcane leaf roll submitted to water deficit stress were analysed. Two cDNA libraries were constructed from plants subjected to 9 and 17 days of water stress. A total of 4639 sequences with good quality (minimum of 100 bases and score 20 according to the quality analysis of Phred program) were clustered using the CAP3 program. Among the clusters, 2077 ESTs were singletons and 2405 ESTs were in 905 clusters containing from 2 to 21 ESTs. Putative regulatory and metabolic proteins related to sugarcane water stress were identified from these 2982 unique transcripts (clusters + singletons) analysed by a similarity search using the NCBI BLASTX algorithm against nonredundant NCBI BLAST protein databases. Based on the NCBI TBLASTX algorithm, 188 unique transcripts were found. These unique transcripts were not similar to the unique transcripts reported by the Sugarcane EST Project from ‘Genoma FAPESP’ Program (SUCEST http://sucest.lad.dcc.unicamp.br/en/), even though these results were obtained from plants grown under different environmental conditions. An analysis of the highest unique transcription frequencies data revealed a set of genes expressing metabolic enzymes such as a lipoxygenase, S-adenosylmethionine synthetase, pyrophosphate-fructose-6-phosphate 1-phosphotransferase and sucrose synthetase. All these enzymes are strictly expressed and appear to be highly related to evolution of drought stress, underlying novelties in sugarcane drought research.
Influência da visão de cores na detecção de frutos, flores e invertebrados em grupos de Callithrix jacchus na Caatinga

Primates can be trichromat. However, this trait is quite variable. While in catarrhine monkeys both males and females have trichromatic vision, in platyrrhines, a color vision plymorphism occurs, with the existence of trichromat and dichromat females, while males are necessarily dichromat. Trichromacy is thought to be an adaptation to improve detection of ripe fruits and/or young leaves against a background of mature leaves. On the other hand, it has been suggested that dichromat individuals perform better in finding camouflaged insects, whereas trichromats may have the advantage of detecting conspicuous insects. Although there are several studies on color vision focused on visual modeling, experiments on semi-natural conditions and studies on nature, the results are inconsistent. Therefore, in this study we analyze whether color vision influences the detection of fruits and insects in groups of Callithrix jacchus in Caatinga. We used visual modeling to calculate the chromatic contrast (JND) between fruits and their backgrounds, and insects and their backgrounds, for all six color vision phenotypes from field photographs. Our results suggest that, fruits in Caatinga can be detected by their brightness and their coloration on the green-red axis in the rainy season, and their coloration on the blueyellow axis and the green-red axis during the dry season. Invertebrates differ from the background through the blue-yellow axis and the green-red axis in the rainy season, and through brightness and the green-red axis in the dry season. We observed that the chromaticity of the background on the red-green axis is constant throughout the year, suggesting an advantage of the trichromats. Our analysis of chromatic contrasts showed that trichromat phenotypes have superior fruit detection performance. As far as insect detection is concerned, all phenotypes are equally able to detect insects. This is the second work on color vision carried out at Caatinga and the first visual modeling work that includes the two main food item types of the calithrichid diet.
Influence of screen based sedentary behaviours on body composition of children

Evidence suggested that children of developed counties are spending huge amount of time with different screen media and it has great impact on children’s physical, mental, and social health. However, enough evidence regarding screen based sedentary behaviour and its health consequences among Indian children has not been found. Thus, the purpose of the study to verify the influence of excessive screen use on body composition of children.The study used a cross-sectional analytical design. 416 boys reading in class-V-and VI (Mean age 11.31 yrs.) of four Government aided school from semi urban areas of North 24 Parganas district in West Bengal, India were included as the subject of the study. Screen time was assessed using self-reported seven day recall questionnaire and Body composition was assessed using skinfold measurement. Descriptive statistics Mean, Standard deviation, Range, Frequency and Percentage were used. Independent –t test and One way Analysis of Variance (ANOVA) followed by Least Significant Difference (LSD) post-hoc test was conducted to understand the influence of Screen based sedentary behaviour on Body composition. Results revealed that majority of the subjects were crossed the recommended Screen time (<2hrs). and the average sum of skinfolds of the entire sample was much higher than normal level. The difference on Body Composition (Sum of Skinfold) among various ST groups was statistically significant at 0.05 level (p<0.05) and lower Screen time groups were almost always better in respect of body composition.
5 Modelling Fluxes of Volatile Fatty Acids from Rumen to Portal Blood

A model was developed that describes the relationships between the production, the ruminal concentrations and the fluxes of volatile fatty acids (VFAs) across portal drained viscera (PDV). This study presents some preliminary results. Firstly, general steady state relationships between production and portal appearance of VFA were determined by fitting equations to published data coupling both intraruminal infusions and measurement of VFA portal fluxes. With a simple model consisting of one digestive and one blood compartment, saturation in uptake of arterial acetate (Ac) by PDV when arterial supply was very good, linearity between production and portal net absorption for each VFA, and saturation in ketogenesis by PDV were evidenced. Secondly, a dynamic model was used to assess the effect of pH on the VFA fluxes in the rumen between two meals (12 h interval). The fractional absorption rate of each VFA by the rumen wall (%/h) was fitted to pH according to their dissociation constant, from data obtained with the emptied washed rumen method. With a diet inducing large postprandial variations of pH, the effects of fractional absorption rate ‐ either constant (related to mean pH) or variable (related to postprandial variations of pH) ‐ on ruminal VFA concentrations and kinetics of VFA absorbed by the rumen wall were quantified.
INFLUENCE OF FENUGREEK SEEDS FLOUR ON THE RHEOLOGICAL CHARACTERISTICS OF WHEAT FLOUR AND BISCUIT QUALITY

Nowadays, demand for health-oriented products such as functional foods which hashigh fiber products is increasing. So, this work studied the effect of partial replacement of wheat flour(72% extraction) by different levels (5%,10%, 15% and 20%) of raw, soaked and germinatedfenugreek seed flour (Trigonella foenum graecum). The chemical and rheological characteristics forproduced dough blends, and on the sensory, physical and chemical characteristics for producedbiscuits were studied. Results indicated that incorporation of fenugreek seed flour (FSF) obviously (P≥0.05) increased in protein, fat, crude fiber, and ash with increasing FSF supplementing levels. Themineral contents of treated fenugreek seed flours almost was higher than the control samples.Germination process of fenugreek seed flour caused a decrease in the most of minerals compared withthe soaking process. The replacement of wheat flour with fenugreek seed flour caused a decrease (P≥0.05) in extensibility of the dough as measured by the extensograph and an increase (P≥ 0.05) inresistance to extension, proportional number and dough energy tests. Farinograph results showed thatall additions of fenugreek seed flour increased water absorption, dough development time and mixingtolerance index, while decreased dough stability and weakening values in the case of higher replacingwith fenugreek seed flour levels. The effects on dough development time, water absorption, andmixing tolerance indices were intensified with GF (germinated fenugreek seed flour) samples under5% or 10% levels. Generally, the addition of germinated fenugreek flour to wheat flour at ratio of 5 or10 levels had a less deleterious effect on the chemical and rheological properties of dough than that ofRF(raw fenugreek seed flour) and/or SF(soaked fenugreek seed flour). The sensory evaluation resultsof supplemented biscuit showed that a maximum of 10% FSF can be incorporated to made acceptablequality biscuits. While, biscuits containing 15 or 20% FSF were unacceptable to the panelists ascompared with the control biscuit. Results of chemical analyses indicated that incorporation of FSFinto biscuits formula obviously (p≥0.05) increased each of protein, fat, crude fiber, ash andindispensable amino acid (IAAs) contents with increasing FSF supplementing levels. The amino acidscomposition revealed that supplemented biscuits with FSF contained the most of IAAs and will covera highly percentages of reference protein pattern of FAO/WHO (1973). Lysine was the first limitingamino acid in control biscuit samples. Supplemented biscuits with germinated FSF had higher lysinecontents than other treatments. It could be concluded that, incorporation up to a 10% level ofgerminated FSF into wheat biscuit formula resulted in improving their chemical, sensory qualitycharacteristics and complementing the deficiency in lysine amino acid.
Investigations of Moon-Magnetosphere Interactions by the Europa Clipper Mission

Haje Korth (1), Robert T. Pappalardo (2), David A. Senske (2), Sascha Kempf (3), Margaret G. Kivelson (4,5), Kurt Retherford (6), J. Hunter Waite (6), Joseph H. Westlake (1), and the Europa Clipper Science Team (1) Johns Hopkins University Applied Physics Laboratory, Maryland, USA, (2) Jet Propulsion Laboratory, California, USA, (3) University of Colorado, Colorado, USA, (4) University of Michigan, Michigan, USA, (5) University of California, California, USA, (6) Southwest Research Institute, Texas, USA. (haje.korth@jhuapl.edu)
Prueba de concepto de una PCR multiplex de primera generación (cualitativa) para detección del oncogén E7 de VPHS de alto riesgo

Introducción: Infección persistente con el virus de papiloma humano de alto riesgo (VPH-AR) causa cáncer de cuello uterino (CCU). Existen ensayos moleculares para la detección y la genotipificación del gen L1 de VPH, sin embargo, L1 puede perderse durante la integración viral. La expresión e integración del oncogén E7 es fundamental para el desarrollo de CCU. Objetivo: Estandarizar una PCR multiplex (mPCR) del oncogén E7 (E7-mPCR) para genotipificación de los VPH-AR de mayor frecuencia en CCU (VPH-16, -18, -31, -33, -45 y -52). Métodos: Se obtuvieron cepillados cervicales de voluntarias y se analizaron amplificando por PCR el gen L1 con subsecuente hibridación reversa. Posteriormente, se escogieron 59 muestras positivas para VPH-AR y se analizaron por E7-mPCR. Resultados: Se evidenció una elevada concordancia entre los resultados del ensayo E7-mPCR y los de la PCR de L1 (concordancia observada de 95,1 %, Kappa de Cohen = 0,88), encontrándose mayor número de infecciones por VPHAR en el 15,8 % con E7-mPCR. Conclusión: E7-mPCR es una herramienta diagnóstica con alta concordancia y económica que puede adaptarse a una plataforma de mayor complejidad para procesar y detectar mayor cantidad de muestras y genotipos de VPH-AR.