Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeting non-canonical nuclear factor-&kgr;B signalling attenuates neovascularization in a novel 3D model of rheumatoid arthritis synovial angiogenesis

Objective. Angiogenesis is crucial in RA disease progression. Lymphotoxin &bgr; receptor (LT&bgr;R)-induced activation of the non-canonical nuclear factor-&kgr;B (NF-&kgr;B) pathway via NF-&kgr;B-inducing kinase (NIK) has been implicated in this process. Consequently, inhibition of this pathway may hold therapeutic potential in RA. We describe a novel three-dimensional (3D) model of synovial angiogenesis incorporating endothelial cells (ECs), RA fibroblast-like synoviocytes (RAFLSs) and RA synovial fluid (RASF) to further investigate the contributions of NF-&kgr;B in this process. Methods. Spheroids consisting of RAFLSs and ECs were stimulated with RASF, the LT&bgr;R ligands LT&bgr; and LIGHT, or growth factor bFGF and VEGF, followed by quantification of EC sprouting using confocal microscopy and digital image analysis. Next, the effects of anginex, NIK-targeting siRNA (siNIK), LT&bgr;R–Ig fusion protein (baminercept) and a novel pharmacological NIK inhibitor were investigated. Results. RASF significantly promoted sprout formation, which was blocked by the established angiogenesis inhibitor anginex (P < 0.05). LT&bgr; and LIGHT induced significant sprouting (P < 0.05), as did bFGF/VEGF (P < 0.01). siNIK pre-treatment of ECs led to reductions in LT&bgr;R-induced vessel formation (P < 0.05). LT&bgr;R–Ig not only blocked LT&bgr;- or LIGHT-induced sprouting, but also RASF-induced sprouting (P < 0.05). The NIK inhibitor blocked angiogenesis induced by LT&bgr;, LIGHT, growth factors (P < 0.05) and RASF (P < 0.01). Conclusion. We present a novel 3D model of synovial angiogenesis incorporating RAFLSs, ECs and RASF that mimics the in vivo situation. Using this system, we demonstrate that non-canonical NF-&kgr;B signalling promotes neovascularization and show that this model is useful for dissecting relative contributions of signalling pathways in specific cell types to angiogenic responses and for testing pharmacological inhibitors of angiogenesis.
What’s new in atopic eczema? An analysis of systematic reviews published in 2009–2010

This review provides a summary of key findings from 18 systematic reviews on atopic eczema, published or indexed between January 2009 and 24 August 2010. There was no good evidence on the possible benefit of organic food consumption and eczema. Maternal intake of fish or fish oil may be associated with a reduced risk of eczema in offspring, although further studies are needed. There is some evidence that partially hydrolysed infant formulas rather than standard formulas may be associated with a reduced risk of eczema in infants, but there are shortcomings in the existing evidence. An inverse relationship has been found between gliomas/acute lymphoblastic leukaemia and allergic disease/eczema, but there appears to be no association between multiple sclerosis and eczema. Attention deficit hyperactivity disorder does appear to be associated with eczema, but there is no evidence of a causal link. The risk of eczema seems to be increased in urban compared with rural areas. Some new evidence has suggested superiority of 1% pimecrolimus over potent and mild corticosteroids at 6 months but not 12 months, and there is some evidence for superiority of 0.03% and 0.1% tacrolimus over 1% pimecrolimus. An updated Cochrane Review still found no evidence of a benefit from any form of antistaphylococcal treatment in managing clinically infected or uninfected eczema. The evidence base is poor for bath emollients, occlusive treatments (e.g. wet and dry wraps) and woven silk clothing in treating eczema. In general, the methods used in most systematic reviews of eczema need to be reported more clearly, especially with regard to a more vigorous quality assessment of included studies. Included studies are frequently heterogeneous, proxy reporting is common, and appropriate disease definitions are often lacking. Better adherence to existing guidance on trial reporting and prospective registration of clinical trials may help improve the quality of studies.
Polymorphism of circadian clock genes and prophylactic lithium response

The therapeutic action of lithium in bipolar mood disorder may be connected with its effect on biological rhythms. In the present study, an attempt was made to investigate an association between multiple single nucleotide polymorphisms (SNPs) and their haplotypes pertaining to four genes involved in regulation of biological rhythms [circadian locomotor output cycle kaput (CLOCK), aryl hydrocarbon receptor nuclear translocator‐like (ARNTL), timeless circadian clock (TIMELESS), period circadian clock 3 (PER 3)], and the efficacy of lithium prophylaxis.
Mechanically strained strained-Si NMOSFETs

The drain-current enhancement of the mechanically strained strained-Si NMOSFET device is investigated for the first time. The improvements of the drain current are found to be /spl sim/3.4% and /spl sim/6.5% for the strained-Si and control Si devices, respectively, with the channel length of 25 /spl mu/m at the external biaxial tensile strain of 0.037%, while the drain-current enhancements are /spl sim/2.0% and /spl sim/4.5% for strained-Si and control Si devices, respectively, with the channel length of 0.6 /spl mu/m. Beside the strain caused by lattice mismatch, the mechanical strain can further enhance the current drive of the strained-Si NMOSFET. The strain distribution due to the mechanical stress has different effect on the current enhancement depending on the strain magnitude and channel direction. The smaller current enhancement for strained-Si device as compared to the control device can be explained by the saturation of mobility enhancement at large strain.
Depression in Cancer Patients attending Outpatients Department of Tertiary Care Hospitals of Karachi

Cancer is an important cause of morbidity and mortality. Globally 14.1 million new cancer cases and 8.2 million deaths due to cancer were reported in 2012. Being diagnosed with cancer is a life challenging experience for most patients and leads to a variety of symptoms like, shock, disbelief, anger, fear, anxiety, guilt , grief and even depression. The rate of depression in cancer patients is estimated to be four times that of the general populaAbstract
Effect of JIANPI HUOXUE decoction on inflammatory cytokine secretion pathway in rat liver with lipopolysaccharide challenge.

AIM To evaluate the effect of Chinese traditional medicinal prescription, JIANPI HUOXUE decoction (JHD) on cytokine secretion pathway in rat liver induced by lipopolysaccharide (LPS). METHODS Twenty-four male SD rats were divided into normal group (n = 4), model group (n = 10) and JHD group (n = 10) randomly. Rats in model group and JHD group were administrated with normal saline or JHD via gastrogavage respectively twice a day for 3 d. One hour after the last administration, rats were injected with LPS via tail vein, 50 mug/kg. Simultaneously, rats in normal group were injected with equivalent normal saline. After LPS stimulation for 1.5 h, serum and liver tissue were collected. Pathological change of liver tissues was observed through hematoxylin-eosin (H.E.) staining. Tumor necrosis factor alpha (TNF-alpha) in serum were assayed by enzyme linked immunosorbent assay (ELISA). The protein expression of TNF-alpha, phosphorylated inhibit-kappaB (p-IkappaB) and CD68 in liver were assayed by Western blot. The distribution of CD68 protein in liver was observed through immunohistochemical staining. The mRNA expression of TNF-alpha, interleukin-6 (IL-6), CD14, toll-like receptor 2 (TLR2) and TLR4 in liver were assayed by real-time RT-PCR. RESULTS Predominant microvesicular change, hepatocyte tumefaction and cytoplasm dilution were observed in liver tissues after LPS administration as well as obvious CD68 positive staining in hepatic sinusoidal. After LPS stimulation, serum TNF-alpha (31.35 +/- 6.06 vs 12225.40 +/- 9007.03, P < 0.05), protein expression of CD68 (1.13 +/- 0.49 vs 3.36 +/- 1.69, P < 0.05), p-IkappaB (0.01 +/- 0.01 vs 2.07 +/- 0.83, P < 0.01) and TNF-alpha (0.27 +/- 0.13 vs 1.29 +/- 0.37, P < 0.01) in liver and mRNA expression of TNF-alpha (1.96 +/- 2.23 vs 21.45 +/- 6.00, P < 0.01), IL-6 (4.80 +/- 6.42 vs 193.50 +/- 36.36, P < 0.01) and TLR2 (1.44 +/- 0.62 vs 4.16 +/- 0.08, P < 0.01) in liver were also increased significantly. These pathological changes were all improved in JHD group. On the other hand, TLR4 mRNA (1.22 +/- 0.30 vs 0.50 +/- 0.15, P < 0.05) was down-regulated and CD14 mRNA increased but not significantly after LPS stimulation. CONCLUSION JHD can inhibit cytokine secretion pathway induced by LPS in rat liver, which is probably associated with its regulation on CD68, p-IkappaB and endotoxin receptor TLR2.
In situ expression of collagen and proteoglycan genes during development of fibrocartilage in bovine deep flexor tendon

A region of fibrocartilage develops in bovine deep flexor tendon where the tissue wraps around bone and is subjected to compressive and shear forces in addition to tension. There is no fibrocartilage at this location in fetal tendon or in adjacent adult tendon that is subjected to tensional load only. We investigated the development of fibrocartilage in tendon using in situ hybridization to localize cells that express collagen and proteoglycan genes typical of either tendon or cartilage. The signal for type I collagen and decorin was high in cells throughout fetal and newborn tendon, as is expected in a growing tissue composed predominantly of type I collagen. No signal for aggrecan was seen in either fetal or newborn tendon. No hybridization with any of the probes for collagen or proteoglycan was detected in cells in the tensional region of adult tendon, indicating that the cells in this tissue are normally quiescent. However, the cells in the fibrocartilage of adult tendon displayed a high level of expression for types I and II collagen, decorin, biglycan, and aggrecan. This suggests that the fibrocartilage in adult tendon is a dynamic tissue. Expression of type IIA collagen is considered a marker of prechondrocytes. Type IIA collagen gene expression was present throughout both the tensional and compressed regions of fetal and newborn tendon but was absent in cartilaga and adult tendon. This suggests that cells located throught fetal tendon may have the capacity to develop as chondrocytes. Fibrocartilage signal was detected for type I collagen in 75% of the cells and for type II collagen in 50% of the cells at one location in adult tendon, suggesting that some cells in this tissue could have expressed mRNA for both type I and type II collagen.
Time Stress and the Processing of Visual Displays

Selecting the appropriate display format for time-constrained tasks is the focus of the research presented in this paper. The effect of time stress on operator performance was assessed by manipulating the time available to process the display. Twenty people were trained as operators and instructed to identify the state of a system using either a digital display or a polygon display. Participants were required to reach a prespecified criterion in training and were then tested under? time-constrained conditions. Time constraints were set at 100%, 50%, and 25% of each person's mean unpaced response times obtained during training. Results showed that response to the time constrained conditions was significantly affected by uncertainty and the type of display format. Discussion focuses on the effects of time stress on performance and the selection of displays for time-constrained tasks.
Experimental columnar metaplasia in the canine oesophagus

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro‐oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro‐oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re‐epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.
Understanding triangulation in research

The term ‘triangulation’ originates in the field of navigation where a location is determined by using the angles from two known points.1 Triangulation in research is the use of more than one approach to researching a question. The objective is to increase confidence in the findings through the confirmation of a proposition using two or more independent measures.2 The combination of findings from two or more rigorous approaches provides a more comprehensive picture of the results than either approach could do alone.3 Triangulation is typically associated with research methods and designs. However, there are several other variations on the term. Triangulation may be the use of multiple theories, data sources, methods …
Filtered Density Function for Large Eddy Simulation of Turbulent Reacting Flows on Unstructured Meshes

A new computational filtered density function (FDF) methodology is developed for large eddy simulation (LES) of turbulent reacting flows on an unstructured mesh. The effect of chemical reactions in the transport equation of FDF appears in a closed form, whereas the effects of scalar mixing and convection within the subgrid are modeled. The FDF transport equation is solved numerically by a particle based Lagrangian Monte Carlo (MC) method. The base filtered transport equations on the unstructured mesh are solved by a finite-volume (FV) method. The consistency of the hybrid FV-MC solver and the realizability of the simulated results are demonstrated via LES of a temporally developing mixing layer. The overall performance of the model is appraised by comparison with direct numerical simulation (DNS) data. Subsequently, the unstructured FDF simulator is employed for predictions of two swirl stabilized non-premixed flames. These are low-swirl (SM1) and high-swirl (SMA2) methane flames. The simulated results are assessed via comparison with experimental data and show excellent agreements. Finally, the unstructured FDF solver is extended to conduct LES of a realistic swirl flame combustor. This is the PRECCINSTA experimental burner from the German Aerospace Center (DLR). The simulated data are analyzed by comparison of the Reynolds-averaged statistics with experimental data and show excellent agreements.
Matrix Metalloproteinases and Their Inhibitors in Exfoliation Syndrome

The purpose of this study was to determine the expression of metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the aqueous humour of patients with exfoliation syndrome (XFS). XFS and control samples were analysed for their MMP content by zymography and for their tissue inhibitors by ELISA. In XFS eyes, an increase for up to 60% in almost all MMPs was observed, as compared to the controls. MMP-2 and MMP-9 were found to predominate. TIMP-1 levels in XFS samples were slightly decreased, while TIMP-2 levels were similar to those of the controls. Our findings suggest that MMPs may be crucial in the progression of XFS, by degrading the abnormal fibrillar matrix components in the anterior segment tissues of XFS eyes. However, the increased levels of MMPs seem not to be able to overcome the overproduction and accumulation of the exfoliative material.
Preventing perinatal transmission of HIV--costs and effectiveness of a recommended intervention.

OBJECTIVE To calculate the national costs of reducing perinatal transmission of human immunodeficiency virus through counseling and voluntary testing of pregnant women and zidovudine treatment of infected women and their infants, as recommended by the Public Health Service, and to compare these costs with the savings from reducing the number of pediatric infections. METHOD The authors analyzed the estimated costs of the intervention and the estimated cost savings from reducing the number of pediatric infections. The outcome measures are the number of infections prevented by the intervention and the net cost (cost of intervention minus the savings from a reduced number of pediatric HIV infections). The base model assumed that intervention participation and outcomes would resemble those found in the AIDS Clinical Trials Group Protocol 076. Assumptions were varied regarding maternal seroprevalence, participation by HIV-infected women, the proportion of infected women who accepted and completed the treatment, and the efficacy of zidovudine to illustrate the effect of these assumptions on infections prevented and net cost. RESULTS Without the intervention, a perinatal HIV transmission rate of 25% would result in 1750 HIV-infected infants born annually in the United States, with lifetime medical-care costs estimated at $282 million. The cost of the intervention (counseling, testing, and zidovudine treatment) was estimated to be $ 67.6 million. In the base model, the intervention would prevent 656 pediatric HIV infections with a medical care cost saving of $105.6 million. The net cost saving of the intervention was $38.1 million. CONCLUSION Voluntary HIV screening of pregnant women and ziovudine treatment for infected women and their infants resulted in cost savings under most of the assumptions used in this analysis. These results strongly support implementation of the Public Health Service recommendations for this intervention.
Enhanced Network Voltage Management Techniques Under the Proliferation of Rooftop Solar PV Installation in Low-Voltage Distribution Network

The proliferation of rooftop solar PV distributed generator (PVDG) installation in a low-voltage distribution network (LVDN) imposes voltage fluctuation challenges that are a threat to distribution system operators. Reactive power control (RPC) methods are insufficient in isolation to combat the overvoltage fluctuations manifested in an LVDN with a significant number of grid-tied PVDG installations, whereas active power curtailment (APC) control can alleviate the voltage fluctuation in such situations and it is achieved at the cost of reduced active power injection. This paper explores how deficiencies in both RPC and APC as separate approaches can be mitigated by suitably combining RPC and APC algorithms. Strategies combining two RPCs and one RPC in conjunction with APC are proposed as two coordinating algorithms by means of an instantaneous measurement of node voltage and active power. These coordinating algorithms are embedded in all the rooftop PVDG grid-tied inverters (GTIs), where the GTI coordinates among them for voltage support without exceeding individual inverter volt-ampere rating. The result of the combined approach shows a significant improvement in managing and stabilizing the voltage and allows the penetration of PVDG to be increased from 35.65% to 66.7% of distribution transformer kilovolt-ampere rating.
Investigation of influence of bearing load and bearing temperature on EDM bearing currents

To detect the worst case and the best case of the bearing operating conditions concerning the magnitude of the high frequency discharge bearing currents (“EDM currents”) and the frequency of electric discharges in the bearings of the small power inverter-fed AC motors, systematic investigations have been performed for three, 4-pole, 1.5 kW squirrel cage induction motors at different speeds, bearing loads and bearing temperatures.
Intraindividual genomic heterogeneity of high‐grade serous carcinoma of the ovary and clinical utility of ascitic cancer cells for mutation profiling

Intraindividual tumoural heterogeneity (ITH) is a hallmark of solid tumours and impedes accurate genomic diagnosis and selection of proper therapy. The aim of this study was to identify ITH of ovarian high‐grade serous carcinomas (OSCs) and to determine the utility of ascitic cancer cells as a resource for mutation profiling in spite of ITH. We performed whole‐exome sequencing, copy number profiling and DNA methylation profiling of four OSC genomes by using multiregional biopsies from 13 intraovarian lesions, 12 extraovarian tumour lesions (omentum/peritoneum), and ascitic cells. We observed substantial levels of heterogeneity in mutations and copy number alterations (CNAs) of the OSCs. We categorized the mutations into ‘common’, ‘shared’ and ‘private’ according to the regional distribution. Six common, eight shared and 24 private mutations were observed in known cancer‐related genes. Common mutations had a higher mutant allele frequency, and included TP53 mutations in all four OSCs. Region‐specific chromosomal amplifications and deletions involving BRCA1, PIK3CA and RB1 were also identified. It is of note that the mutations detected in ascitic cancer cells represented 92.3–100% of overall somatic mutations in the given case. Phylogenetic analyses of ascitic genomes predicted a polyseeding origin of somatic mutations in ascitic cells. Our results demonstrate that, despite ITH, somatic mutations, CNAs and DNA methylations in both ‘common’ category and cancer‐related genes were highly conserved in ascitic cells of OSCs, highlighting the clinical relevance of genome analysis of ascitic cells. Ascitic tumour cells may serve as a potential resource for discovering somatic mutations of primary OSC with diagnostic and therapeutic relevance. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transcriptional Regulation of the Pituitary Vasopressin V1b Receptor Involves a GAGA-binding Protein*

The role of CT repeats (inverted GAGA box) in the rat vasopressin V1b receptor (V1bR) promoter in the transcriptional regulation of this gene was studied in H32 hypothalamic cells, which express endogenous V1bR. Transfection of a 2.5-kb V1bR fragment (2161 bp upstream and 377 bp downstream of the proximal transcriptional start point) into a luciferase vector (V1bRp2.5-Luc) results in promoter activity in these cells. The 670-bp proximal promoter fragment containing the GAGA box showed maximal promoter activity, whereas deletion of the GAGA box abolished transcription.Drosophila GAGA-binding protein increased V1bR promoter activity by 11-fold when cotransfected with V1bRp2.5-Luc and increased endogenous V1bR expression. Electrophoretic mobility shift assay showed specific binding of pituitary nuclear extracts to radiolabeled GAGA oligonucleotides, which increased following restraint stress in rats, a condition associated with V1bR up-regulation. DNA-binding activity involved a protein complex because it was abolished by deoxycholate. Size-exclusion column chromatography showed a complex of 127 kDa, which dissociated into ∼70-kDa components after deoxycholate/Nonidet P-40 treatment. This study demonstrates that interactions of GAGA-binding proteins with the GAGA box of the V1bR promoter activate V1bR gene expression and provides a potential mechanism for physiological regulation of V1bR transcription.