Miracle-dz/UniFAR-FTUs huggingface dataset:
Soluble CD146 boosts therapeutic effect of endothelial progenitors through proteolytic processing of short CD146 isoform.

AIMS Endothelial colony-forming cells (ECFC) constitute an endothelial progenitor fraction with a promising interest for the treatment of ischaemic cardiovascular diseases. As soluble CD146 (sCD146) is a new factor promoting angiogenesis, we examined whether sCD146 priming could improve the therapeutic potential of ECFC and defined the involved mechanism. METHODS AND RESULTS We investigated the effects of sCD146 priming on regenerative properties of ECFC in vivo. In a mouse model of hindlimb ischaemia, the homing of radiolabelled cells to ischaemic tissue was assessed by SPECT-CT imaging. Soluble CD146 priming did not modify the number of engrafted ECFC but improved their survival capacity, leading to an enhanced revascularization. The mechanism of action of sCD146 on ECFC was studied in vitro. We showed that sCD146 acts in ECFC through a signalosome, located in lipid rafts, containing angiomotin, the short isoform of CD146 (shCD146), VEGFR1, VEGFR2, and presenilin-1. Soluble CD146 induced a sequential proteolytic cleavage of shCD146, with an extracellular shedding followed by an intramembrane cleavage mediated by matrix metalloprotease (MMP)/ADAM and presenilin-1, respectively. The generated intracellular part of shCD146 was directed towards the nucleus where it associated with the transcription factor CSL and modulated the transcription of genes involved in cell survival (FADD, Bcl-xl) and angiogenesis (eNOS). This effect was dependent on both VEGFR1 and VEGFR2, which were rapidly phosphorylated by sCD146. CONCLUSIONS These findings establish that activation of the proteolytic processing of shCD146, in particular by sCD146, constitutes a promising pathway to improve endothelial progenitors' regenerative properties for the treatment of cardiovascular diseases.
Inhibition of p38 activity reverses claudin‐6 induced cell apoptosis, invasion, and migration

Background Claudin‐6 is a protein component of tight junctions and its expression could downregulate the malignant phenotype of breast carcinoma. Here we investigated the mechanisms of claudin‐6 induced human MCF‐7 breast cancer cells apoptosis, invasion, and migration. Methods Terminal deoxyribonucleotide transferase‐mediated nick‐end labeling assay and Annexin‐V/PI double stain assay were carried out to evaluate apoptosis. Inhibitors of each pathway were used to inactivate the signaling pathways. The expression of claudin‐6 and phosphate p38, Erk 1/2 and Akt protein levels was confirmed by Western blotting analysis. Invasive and migratory traits of claudin‐6 expressing cells were determined by Boyden chamber invasion assay and monolayer wound‐healing assay. Results Cells with high‐level expression of claudin‐6 had a higher rate of apoptosis than control cells. Western blotting assay showed that by contrast to control groups, p38 pathways were more activated in claudin‐6 expressing cells. However, after inhibitor SB203580 treatment, the activation status could be significantly counteracted. Furthermore, by applying inhibitors to the apoptotic rate, invasive and migratory traits were also recovered in cells with claudin‐6 expression. Conclusion Claudin‐6 may function through p38 mitogen‐activated protein kinase pathway, of which inhibition may reverse claudin‐6‐induced cell apoptosis, invasion, and migration.
Ultrastructural localization of an intracellular Toxoplasma protein that induces protection in mice

We report the ultrastructural localization of Toxoplasma antigens recognized by monoclonal antibody F3G3, which protects mice against lethal challenge. By using colloidal immunogold labeling, F3G3 failed to react with the surface of intact Toxoplasma cells, confirming previous observations that it recognizes an intracellular antigen. Immunoperoxidase labeling with F3G3 was obtained only when Toxoplasma cells were previously exposed to Triton X-100. A specific immunoperoxidase reaction was located beneath the surface membrane in the region of the pellicle and within the elaborate network of vesicles which are extruded from the surface of Toxoplasma cells during entry into host cells. Similar results were obtained with mouse polyclonal sera and a second monoclonal antibody, 6-86-1E11, both of which were produced against the F3G3 affinity-purified protein. The location of the epitope recognized by F3G3 was confirmed by purifying T. gondii-derived surface membrane vesicles, separating these proteins by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and immunoblotting. Monoclonal antibody 6-86-1E11 and the analogous polyclonal sera reacted with the antigenically related proteins of 58 and 28 kilodaltons that were found both in the intact organisms and in the purified surface membrane vesicles. These results indicate that the epitope recognized by F3G3 is located beneath the Toxoplasma cell surface membrane and is contained within plasma membrane-derived vesicles.
A cohort study of the prevalence of sleep problems in adults with intellectual disabilities

Previous studies of the prevalence of sleep problems in adults with intellectual disabilities (ID) are affected by small, potentially biased samples and other limitations. This study aims to determine the prevalence and associations of sleep problems in the adult population with ID. The 4‐week period prevalence of sleep problems was determined in a cross‐sectional study of all adults with ID in a defined geographical area. Sleep problems were identified using the Psychiatric Assessment Scale for Adults with Developmental Disabilities (PAS‐ADD) checklist and categorized as initial insomnia, early morning wakening and broken sleep. A fourth, composite, variable of significant sleep problem was also derived. Of the 1023 adults with ID who participated, 9.2% had experienced a significant sleep problem, during the 1‐month period. Individuals with a significant sleep problem are more likely to have mental ill‐health [odds ratio (OR) = 5.53, 95% confidence interval (CI) 3.52–8.69], problem behaviours (OR = 2.06, 95% CI: 1.25–3.41) and respiratory disease (OR = 2.03, 95% CI: 1.27–3.26). There is a positive association between visual impairment and initial insomnia (OR = 1.91, 95% CI: 1.21–3.04). Although a diagnosis of epilepsy is not associated with sleep problems, the finding that individuals taking antiepileptic medication are more likely to experience broken sleep (OR = 1.73, 95% CI: 1.13–2.66) suggests that medication side effects may impact on sleep of individuals with ID. The results suggest that there is a need to further examine the relationship between sleep problems and co‐morbid health problems, which would inform the development of interventions, and trials of their efficacy.
L‐Glutamate and Insulin Enhance Glycogen Synthesis in Cultured Astrocytes from the Rat Brain Through Different Intracellular Mechanisms

Abstract: The effects of L‐glutamate and insulin on glycogen synthesis in astrocytes were examined. L‐Glutamate and insulin both stimulated glycogen synthesis in primary cultures of rat astrocytes in a dose‐dependent manner, as measured by the incorporation of 14C from [14C]glucose into glycogen. D‐Aspartate also increased the incorporation of 14C into glycogen. When insulin and L‐glutamate were added together, the glycogen synthesis as well as glycogen content of the cells was additively increased. Wortmannin, an inhibitor of phosphatidylinositol 3‐kinase, had little effect on glycogen synthesis induced by L‐glutamate, whereas it suppressed the insulin‐induced glycogen synthesis. These results suggest that the insulin‐ and L‐glutamate‐induced glycogen syntheses are mediated by different intracellular mechanisms. In fact, insulin stimulated the conversion of glycogen synthase b to glycogen synthase a, which was suppressed by wortmannin. L‐Glutamate and D‐aspartate, however, did not increase the level of glycogen synthase a activity. By contrast, L‐glutamate increased 2‐deoxy‐D‐[3H]glucose uptake by the astrocytes, whereas insulin did not affect the uptake. These results suggest that insulin stimulates glycogen synthesis in astrocytes by activating glycogen synthase, which is dependent on a wortmannin‐sensitive signaling pathway. L‐Glutamate, however, enhances the glucose uptake, which contributes to the increase in glycogen synthesis in the cells.
Nf1 mutant mice with p19ARF gene loss develop accelerated hematopoietic disease resembling acute leukemia with a variable phenotype

Juvenile Myelomonocytic Leukemia (JMML) is a relentlessly progressive myeloproliferative/myelodysplastic (MPD/MDS) hematopoietic disorder more common in patients with any one of at least three distinct genetic lesions, specifically NF1 gene loss and PTPN11 and NRAS mutations. NF1 and PTPN11 are molecular lesions associated with Neurofibromatosis Syndrome Type I (NF1 Syndrome) and Noonan's Syndrome, respectively. The occurrence of JMML is rare; even among those predisposed with these syndromes to development of disease, and secondary genetic events likely contribute to the development and progression of disease. In NF1 syndrome, loss of p53 function is a common event in solid tumors, but uncommon in JMML, suggesting that the p53 pathway may be modified by other events in this hematopoietic disorder. The work presented here investigates the possible role of the p19Arf (p19) tumor suppressor in development of MPD associated with Nf1 gene loss in mice. We find that Nf1 mutant hematopoietic cells with loss of p19 develop accelerated hematopoietic disease similar to acute leukemia with a variable phenotype. This suggests that p19 may play a role in development of JMML and evaluation of the human p19 homolog (p14ARF) in JMML may be informative. Am. J. Hematol. 86:579–585, 2011. © 2011 Wiley‐Liss, Inc.
Strategies for estimating behavioural frequency in survey interviews.

When people answer survey questions of the form "During the past month, how many times did you. " their responses provide valuable data for researchers and policy makers. Yet the way respondents produce their answers to these "behavioural frequency questions" is not well understood. This article demonstrates that survey respondents can use an array of distinct estimation strategies, depending on what information is available in their memories. The kind of event information that people use is related to factors such as the regularity of occurrence, similarity of one episode to the next, and frequency. In a study conducted as a telephone survey, respondents' verbal reports and response-time patterns indicate that they usually answer behavioural frequency questions by either retrieving and counting episodes, retrieving or estimating rates of occurrence, or converting a general impression of frequency into a numerical quantity. The third strategy should be of particular concern to survey researchers because respondents provide a quantitative estimate without any relevant numerical knowledge. The set of strategies and the factors that influence their use are integrated into a statistical model that could help survey practitioners to improve data quality and memory researchers to broaden their perspective.
Transmission through and wave guidance on metal plates perforated by periodic arrays of through‐holes of subwavelength coaxial cross‐section

Perfect electrically conducting (PEC) plates perforated by doubly periodic arrays of through‐holes of subwavelength coaxial cross‐section permit enhanced transmission of plane waves and support surface wave guidance. The transmission enhancement is attributed to coupling of free‐space fields to TEM and TE11 modal fields in holes and occurs via two distinct mechanisms. The first couples incident fields to local resonances (cavity modes) supported by individual holes. The second couples scattered fields (diffraction modes) to global resonances (surface waves). The surface waves arise due to strong interactions between the holes and can have a large propagation wavenumber. The presented PEC model is adequate in the microwave and terahertz regimes and insights into related wave phenomena at optical frequencies. © 2007 Wiley Periodicals, Inc. Microwave Opt Technol Lett 49: 1554–1558, 2007; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mop.22484
THE α1b-ADRENERGIC RECEPTOR SUBTYPE: MOLECULAR PROPERTIES AND PHYSIOLOGICAL IMPLICATIONS

ABSTRACT The aim of this review is to summarize some of the main findings from our laboratory as well as from others concerning the biochemical, molecular, and functional properties of the α1b-adrenergic receptor. Experimental and computational mutagenesis of the α1b-adrenergic receptor have been instrumental in elucidating some of the molecular mechanisms underlying receptor activation and receptor coupling to Gq. The knockout mouse model lacking the α1b-adrenergic receptor has highlighted the potential implication of this receptor subtype in variety of functions including the regulation of blood pressure, glucose homeostasis, and the rewarding response to drugs of abuse.
Ocular Surface Findings in Hallopeau-Siemens Subtype of Dystrophic Epidermolysis Bullosa: Report of a Case and Literature Review

Purpose: This article describes the clinical features and long-term changes in corneal sensitivity, tear function, and impression cytology findings in a patient with recessive dystrophic epidermolysis bullosa (DEB). Methods: The patient underwent best-corrected Landolt visual acuity measurements, slit-lamp examinations, anterior segment photography, Schirmer test with anesthesia, tear film break-up time, corneal fluorescein and Rose-Bengal staining, assessment of corneal sensitivity, and conjunctival impression cytology at the initial and final visits. Results: The patient had a recurrent corneal erosion in the right eye and a painful corneal blister with extensive superficial punctuate keratopathy in the left eye, which remained refractory to treatment with patching, lubricants, and antibiotic ointments for 10 weeks. The corneal disease in both eyes responded swiftly to topical fibronectin, topical nonpreserved tears, vitamin A ointment, and therapeutic soft contact lenses. Maintenance treatment was continued with preservative-free topical tear drops and vitamin A ointment. Corneal disease did not recur in the patient during the follow-up of 29 months. The mean corneal sensitivity and tear film break-up time were decreased initially in both eyes and attained normal values with treatment. Impression cytology revealed squamous metaplasia, loss of cellular cohesion, and total absence of goblet cells before treatment, all of which were observed to be normalized at the final follow-up. Conclusions: The ocular surface disease in DEB was characterized by low corneal sensitivity, disorder of tear quality, decreased cellular cohesion, squamous metaplasia of the conjunctiva, and goblet cell loss. Close follow-up for ocular complications in DEB is essential and a pathophysiology-oriented approach to the epithelial disease may not only provide rapid healing but might prevent recurrences as well.
Intraoperative Blood Salvage During Liver Transplantation in Patients With Hepatocellular Carcinoma: Efficiency of Leukocyte Depletion Filters in the Removal of Tumor Cells

Background. Intraoperative blood salvage (IBS) reduces homologous transfusion in orthotopic liver transplantation (OLT), but may carry with it the risk of reinfusing tumor cells in patients with hepatocellular carcinoma (HCC). The use of leukocyte depletion filters (LDFs) for the removal of tumor cells is rarely reported in clinical OLT. The aims of this study were to evaluate the frequency of tumor cell contamination in surgical field during OLT for HCC recipients and to investigate the efficiency of additional LDFs for eliminating tumor cells from IBS. Methods. Thirty-two HCC patients with preoperatively elevated serum alpha-fetoprotein (AFP) underwent OLT. The blood from the surgical field was collected and processed by an autotransfusion device (Cell Saver 5), followed by 2 consecutive LDF filtrations. The HCC cells in IBS samples and filtered samples were determined using a nested RT-PCR technique to detect the AFP mRNA. Results. The shed blood samples from 20 (62.5%) of the 32 HCC patients were contaminated with HCC cells and 15 of them remained positive after Cell Saver processing. Patients within the Milan or UCSF criteria were less likely to have HCC cell contamination and the contaminated HCC cells were more likely to be removed by the Cell Saver in these patients as compared to other patients (P<0.01). After filtration through an additional LDF, most cases (13/15) became negative except for those with ruptured tumors (P<0.05). Conclusions. Our results suggest that blood filtration with the LDF can efficiently remove tumor cells and the use of an additional LDF after use of the Cell Saver could markedly reduce the risk of tumor cell reintroduction during the OLT in HCC recipients with nonruptured tumors.
Enhancing Nonhuman Primate Care and Welfare Through the Use of Positive Reinforcement Training

Nonhuman primates are excellent subjects for the enhancement of care and welfare through training. The broad range of species offers tremendous behavioral diversity, and individual primates show varying abilities to cope with the stressors of captivity, which differ depending on the venue. Biomedical facilities include small single cages, pair housing, and breeding corrals with large social groups. Zoos have social groupings of differing sizes, emphasizing public display and breeding. Sanctuaries have nonbreeding groups of varying sizes and often of mixed species. In every venue, the primary objective is to provide good quality care, with minimal stress. Positive reinforcement training improves care and reduces stress by enlisting a primate's voluntary cooperation with targeted activities, including both husbandry and medical procedures. It can also improve socialization, reduce abnormal behaviors, and increase species-typical behaviors. This article reviews the results already achieved with positive reinforcement training and suggests further possibilities for enhancing primate care and welfare.
Impact of changing trends in technique and learning curve on outcome of hypospadias repair: An experience from tertiary care center

Introduction: Apart from numerous clinical factors, surgical experience and technique are important determinants of hypospadias repair outcome. This study was aimed to evaluate the learning curve of hypospadias repair and the impact of changing trends in surgical techniques on the success of primary hypospadias repair. Materials and Methods: We retrospectively analyzed of data of 324 patients who underwent primary repair of hypospadias between January 1997 and December 2013 at our center. During the initial 8 years, repairs were performed by multiple 5 different urologists. From 2005 onwards, all procedures were performed by a single urologist. The study cohorts was categorized into three groups; Group I, surgeries performed between 1997–2004 by multiple surgeons, Group II, between 2005–2006 during the initial learning curve of a single surgeon, and Group III, from 2007 onwards after completion of the learning curve of the single surgeon. The groups were compared in respect to surgical techniques, overall success and complications. Results: Overall 296 patients fulfilled the inclusion criterion, 93 (31.4%), 50 (16.9%), and 153 (51.7%) in Group I, II, and III, respectively. Overall success was achieved in 60 (64.5%), 32 (64%), and 128 (83.7%) patients among the three groups respectively (P < 0.01). Nineteen (20.4%), 20 (40%), and 96 (62.7%) patients underwent tubularized incised plate repair in Group I, II, and III, with successful outcome in 12 (63.2%), 15 (75%), and 91 (94.8%) patients, respectively (P < 0.01). The most common complication among all groups was urethrocutaneous fistula, 20 (21.5%) in Group I, 11 (22%) in Group II, and 17 (11.1%) in Group III. Conclusion: There is a learning curve for attaining surgical skills in hypospadias surgery. Surgeons dedicated for this surgery provide better results. Tubularized incised plate urethroplasty appear promising in both distal and proximal type hypospadias.
Dose accuracy and durability of a durable insulin pen before and after simulated lifetime use

Abstract Background and objective: NovoPen Echo is an insulin pen designed specifically for children and adolescents with diabetes. The pen combines half-unit dosing and a simple memory function that records the size of the last dose and the time in hours that has elapsed since last injection. Durability is an essential feature of durable insulin pens in order to ensure accuracy throughout the lifetime of the pen. This study was designed to assess dose accuracy and durability of NovoPen Echo before and after simulated lifetime use. *NovoPen Echo is a registered trademark of Novo Nordisk A/S, Bagsvaerd, Denmark. Research design and methods: All testing was conducted according to International Organization for Standardization (ISO) guideline 11608-1 for pen injectors. Dose accuracy was measured for the delivery of 0.5 international units (IU) (5 mg), 15 IU (150 mg) and 30 IU (300 mg) test medium before and after lifetime simulation under standard, cool and hot conditions. Functionality tests were also performed under a number of stress conditions including dry heat, cyclical temperature, vibration, free fall and electrostatic discharge. **1IU for human insulin corresponds to 1U for modern insulin. Results: The dose accuracy of NovoPen Echo meets the requirement stated in ISO 11608-1 for all three doses for all tests before and after lifetime simulation. The pens remained intact and retained dosing accuracy at all doses after exposure to variations in temperature and humidity and before and after physical challenge to simulate lifetime use. Conclusions: The accuracy of NovoPen Echo was retained under conditions of stress likely to be encountered in everyday use due to its durable design.
Ray Tracing Based 60 GHz Channel Clustering and Analysis in Staircase Environment

Channel modeling is of vital importance to the development and performance evaluation of wireless communication systems. Though many millimeter-wave (mmWave) channel models have been proposed, few of them concern about staircase environments. This paper analyzes the statistical characteristics of 60 GHz channels in a staircase environment with the transmitter (Tx) side fixed and the receiver (Rx) side moving, especially the variation of characteristics arising from the motion of receiver Rx. Fuzzy c-means (FCM) algorithm is applied in clustering procedure and the Kim-Park (K-P) index combined with the multipath component distance (MCD) are utilized to obtain the optimal cluster number. Simulation results show that almost all of the channel characteristics are related to the Euclidean distance between the Tx and Rx. Also, they are affected by building structures, which will provide guidance on the layout of communication devices.