Miracle-dz/UniFAR-FTUs huggingface dataset:
The Vascular Perspective of Systemic Sclerosis: Of Chickens, Mice and Men

Systemic sclerosis (SSc), or scleroderma, is an autoimmune connective tissue disease characterized by structural and functional vascular abnormalities, perivascular mononuclear cell infiltration, and increased deposition of extracellular matrix in skin and internal organs. The initial stages of SSc are generally not accessible for analysis in man, therefore, the availability of appropriate animal models is of great importance for the elucidation of the pathogenesis of this disease. UCD–200 chickens show the entire clinical, histopathological and serological spectrum of SSc, whereas tight skin (Tsk)1/+ and Tsk2/+ mice, other animal models of scleroderma, lack the vascular injury. A parallel comparative study of skin biopsies of UCD–200 chickens and human SSc patients revealed that endothelial cell apoptosis, induced by anti–endothelial cell antibody (AECA)– dependent cellular cytotoxicity, is a primary event in the pathogenesis of SSc. This review focuses on recently established data on endothelial cell injury in animals with spontaneous disease and humans, AECA, adhesion molecules and cytokine profiles that support a vascular pathogenesis in scleroderma.
Professor Sir William Liley (1929–83): New Zealand Perinatal Physiologist

William (Bill) Liley received his MB ChB from Otago University, Dunedin (New Zealand), in 1954. Under the guidance of the neurophysiologist Professor J C Eccles (1903–97), he carried out major research on neuromuscular transmission, both as an undergraduate at Otago University and as a postgraduate at the Australian National University at Canberra. In 1957 Bill Liley switched to research in obstetrics at the Women's National Hospital at Auckland in New Zealand. He refined the diagnostic procedure for rhesus haemolytic disease of the newborn and was able to predict its severity. Liley developed the technique of intrauterine transfusion of rhesus-negative blood for severely affected fetuses and led the team that carried out the first successful fetal transfusions in the world. He was a passionate advocate of the medical and societal rights of the unborn child.
Analyse et simulation cinématique du mouvement du bras lors de la manipulation d'un objet pour la simulation ergonomique à l’aide d’un mannequin numérique

Le travail de these expose dans ce manuscrit s'interesse a la simulation d'un mouvement de manipulation d'objet, plus particulierement a la saisie suivie de la rotation d'une sphere selon un axe fixe. Le but ici est, a partir d'une analyse de mouvements reels, d'etre capable de proposer un algorithme de simulation reproduisant des mouvements comparables aux donnees experimentales, en fournissant en entree le moins d'informations possibles et en essayant d'introduire de la variabilite dans le mouvement simule. 12 sujets volontaires ont participe a l'experimentation. Nous leur avons demande de saisir et de tourner une sphere de 60mm de diametre avec des amplitudes allant de 45° a 360°, dans les deux sens. L'analyse de ces donnees experimentales, completee par des simulations de l'effet des limites articulaires sur le mouvement nous ont permis d'etudier plusieurs hypotheses sur le controle de mouvement telles que l'hypothese de confort final (« end-state comfort ») et le principe de travail minimum. Une des conclusions majeures est que l'anticipation posturale au moment de saisie semble etre expliquee davantage par le confort en fin de mouvement qu'au moment de saisie. Base sur ces observations, nous proposons un algorithme de simulation avec pour nouveautes la prise en compte de l'espace de mouvements admissibles par les limites articulaires ainsi que l'introduction de la variabilite au choix de la posture de saisie. Les premiers resultats semblent etre en accord en grande partie avec les observations experimentales donnant une base de travail pour aller vers des outils de simulation se rapprochant de plus en plus vers un comportement "humain"
Phosphatidylinositol 4,5-Bisphosphate Is Acting as a Signal Molecule in α1-Adrenergic Pathway via the Modulation of Acetylcholine-activated K+ Channels in Mouse Atrial Myocytes*

We have investigated the effect of α1-adrenergic agonist phenylephrine (PE) on acetylcholine-activated K+ currents (I KACh). I KACh was recorded in mouse atrial myocytes using the patch clamp technique.I KACh was activated by 10 μm ACh and the current decreased by 44.27 ± 2.38% (n = 12) during 4 min due to ACh-induced desensitization. When PE was applied with ACh, the extent of desensitization was markedly increased to 69.34 ± 2.22% (n = 9), indicating the presence of PE-induced desensitization. I KAChwas fully recovered from desensitization after a 6-min washout. PE-induced desensitization of I KACh was not affected by protein kinase C inhibitor, calphostin C, but abolished by phospholipase C (PLC) inhibitor, neomycin. When phophatidylinositol 4,5-bisphosphate (PIP2) replenishment was blocked by wortmannin (an inhibitor of phophatidylinositol 3-kinase and phophatidylinositol 4-kinase), desensitization ofI KACh in the presence of PE was further increased (97.25 ± 7.63%, n = 6). Furthermore, the recovery from PE-induced desensitization was inhibited, and the amplitude of I KACh at the second exposure after washout was reduced to 19.65 ± 2.61% (n = 6) of the preceding level. These data suggest that the KAChchannel is modulated by PE through PLC stimulation and depletion of PIP2.
Vancomycin for Staphylococcus aureus endocarditis in intravenous drug users

The clinical courses of 13 consecutive intravenous drug users with Staphylococcus aureus endocarditis treated principally with vancomycin were reviewed. Two patients, one with only right-sided endocarditis and the other with tricuspid and mitral valve endocarditis, had recurrences of positive blood cultures 2 days after completing a 4-week course of vancomycin. Two patients, both of whom eventually were cured, had modifications of therapy because of bacteremia persisting 7 and 16 days into therapy. One patient required an operation for recurrent fevers, and the resected vegetation showed evidence of active infection. Time-kill studies performed with nafcillin and vancomycin for 10 isolates of S. aureus showed that vancomycin was less rapidly bactericidal than nafcillin. Although vancomycin is used as an alternative to penicillinase-resistant penicillins for treatment of staphylococcal endocarditis, these findings raise the question of whether it is equivalent to these drugs in efficacy.
Small Sample Size Effects in Statistical Pattern Recognition: Recommendations for Practitioners

The effects of sample size on feature selection and error estimation for several types of classifiers are discussed. The focus is on the two-class problem. Classifier design in the context of small design sample size is explored. The estimation of error rates under small test sample size is given. Sample size effects in feature selection are discussed. Recommendations for the choice of learning and test sample sizes are given. In addition to surveying prior work in this area, an emphasis is placed on giving practical advice to designers and users of statistical pattern recognition systems. >
Multiplicity and transverse momentum dependence of two- and four-particle correlations in pPb and PbPb collisions

Measurements of two- and four-particle angular correlations for charged particles emitted in pPb collisions are presented over a wide range in pseudorapidity and full azimuth. The data, corresponding to an integrated luminosity of approximately 31 nb − 1 , were collected during the 2013 LHC pPb run at a nucleon–nucleon center-of-mass energy of 5.02 TeV by the CMS experiment. The results are compared to 2.76 TeV semi-peripheral PbPb collision data, collected during the 2011 PbPb run, covering a similar range of particle multiplicities. The observed correlations are characterized by the near-side ( | (cid:3)φ | ≈ 0) associated pair yields and the azimuthal anisotropy Fourier harmonics ( v n ). The second-order ( v 2 ) and third-order ( v 3 ) anisotropy harmonics are extracted using the two-particle azimuthal correlation technique. A four-particle correlation method is also applied to obtain the value of v 2 and further explore the multi-particle nature of the correlations. Both associated pair yields and anisotropy harmonics are studied as a function of particle multiplicity and transverse momentum. The associated pair yields, the four-particle v 2 , and the v 3 become apparent at about the same multiplicity. A remarkable similarity in the v 3 signal as a function of multiplicity is observed between the pPb and PbPb systems. Predictions based on the color glass condensate and hydrodynamic models are compared to the experimental results.
Phosphoinositide 3-kinase in immunological systems.

Phosphoinositide 3-kinases (PI3Ks) are an evolutionarily conserved family of signal transducing enzymes. A great variety of stimuli activate PI3K, leading to the transient accumulation of its lipid products in cell membranes. These lipids serve as second messengers to regulate the location and activity of an array of downstream effector molecules. In cells of the mammalian immune system, PI3K is activated by receptors for antigen, cytokines, costimulatory molecules, immunoglobulins and chemoattractants. Signaling via PI3K regulates immune cell proliferation, survival, differentiation, chemotaxis, phagocytosis, degranulation, and respiratory burst. Here we review our current understanding of PI3K signaling in leukocytes.
On the bootstrap current in stellarators and tokamaks

The expression for the long-mean-free-path limit of the bootstrap current in stellarators is rederived in such a way that the expansion procedure is identical to that used in the corresponding calculation for a tokamak. In addition, the first correction due to finite collisionality is calculated and shown to vanish in quasi-isodynamic configurations without net current. This correction, which is proportional to the square root of the collisionality, is found to compare well with a numerical solution of the first-order drift kinetic equation in spherical tokamak geometry. Numerically, it appears that there is a similar correction in general stellarator geometry, which however depends on the strength of the radial electric field.
Disrespect and Isolation: Elder Abuse in Chinese Communities*

ABSTRACT Based on a qualitative study of home care workers, this paper aims to understand elder abuse of Chinese Canadians. The findings show disrespect is the key form elder abuse takes in the Chinese community. As a culturally specific form of abuse, disrespect remains invisible under categories of elder abuse derived from a Western cultural perspective. Applying a social exclusion framework to understand the dynamic of elder abuse, we argue that as a marginalized racial minority immigrant, an elderly Chinese person's vulnerability to abuse is increased under conditions of social isolation. RÉSUMÉ Basé sur une étude qualitative portant sur les soins à domicile, cet article vise à comprendre les mauvais traitements infligés aux sino-canadiens âgés. Les résultats montrent que, au sein de la communauté chinoise, les mauvais traitements prennent le plus souvent la forme d'un manque de respect. En tant que forme d'abus spécifique à une certaine culture, le manque de respect est un mauvais traitement qui demeure invisible lorsqu'on l'analyse dans une perspective culturelle occidentale. En nous servant d'un cadre centré sur l'exclusion sociale pour comprendre la dynamique des abus infligés aux aînés, nous soutenons que, en tant que minorité raciale d'immigrants marginalisés, les personnes âgées d'origine chinoise sont particulièrement vulnérables aux mauvais traitements dans un contexte d'isolement social.
Amniotic Membrane Transplantation for Intraoperative Conjunctival Repair During Trabeculectomy With Mitomycin C

PurposeTo describe the use of amniotic membrane (AM) transplantation for the repair of conjunctival buttonholes during trabeculectomy with mitomycin C. MethodsFour eyes of 3 patients with thin conjunctiva, precluding watertight conjunctival closure at the incision site with suturing, underwent intraoperative AM grafts over the leaking areas. ResultsIn all eyes, a functional, nonleaking bleb was achieved. At the latest follow-up (8 to 30 mo), all eyes had intraocular pressures of 12 mm Hg or less without medications. ConclusionsAM transplantation was effective in the intraoperative closure of conjunctival buttonholes which developed at the incision line in 4 eyes. This intervention may be a useful addition to the glaucoma surgeon's repertoire of surgical techniques.
SIMULACIÓN DE UN ESCURRIMIENTO REACTIVO AL INTERIOR DE UNA CÁMARA DE COMBUSTIÓN REACTIVE FLUID FLOW SIMULATION INSIDE COMBUSTION CHAMBER

RESUMEN El presente trabajo dice relacion con la simulacion de gases calientes al interior de una camara de tubular combustion. Siendo asi, se generan mallas en dominios tubulares curvilineos. La inyeccion de combustible es realizada a traves de un cuerpo esferico posicionado en el eje de simetria de la camara afectado por un ﬂujo primario axial y un ﬂujo secundario radial. El ﬂuido es considerado newtoniano incompresible y con propiedades termofisicas constantes, en cuanto el ﬂujo es considerado laminar, modelado a traves de la ecuaciones de Navier-Stokes. La formulacion de Shvab-Zel’dovich es utilizada para modelar el transporte de energia y especies a traves de una variable denominada Potencial de Acoplamiento. El modelo matematico es resuelto numericamente a traves del Metodo de los Volumenes Finitos descrito en coordenadas curvilineas con arreglo colocalizado de variables. Los terminos difusivos son representados por diferencias centradas y se usa el esquema WUDS para los terminos convectivos. La integracion temporal es del tipo implicito. Resultados de campos de velocidades, temperaturas y concentraciones son mostrados y comparados con datos encontrados en la literatura especializada. Se concluye en cuanto a la calidad cualitativa y cuantitativa de los resultados generados y en particular en lo que dice relacion con la forma de la llama.Palabras clave: Simulacion, combustion, volumenes ﬁnitos, camara, modelo numerico.
Cryopreservation of cells does not substantially alter the DNA methylome of CD3+CD4+ T cells

Epigenetic signatures vary between cells (1), and many research groups have moved to analysis of cell subsets rather than mixed cell populations such as whole blood, to simplify the interpretation of epigenetic studies. It is not always practical to extract individual cell populations on fresh samples, and hence it is becoming more common that research groups cryopreserve peripheral blood mononuclear cells (PBMCs) from study participants for later cell separation and use in epigenetic studies. DNA methylation is known to be altered by the environment, including techniques such as long-term cell culture (2); however, the effect of cryopreservation of cells on the methylome has not previously been investigated. Therefore, in this study we compared genome-wide DNA methylation levels in CD3+CD4+ T cells separated from fresh and cryopreserved PBMC samples from the same healthy individuals using the HumanMethylation450 BeadChip Kit (Illumina, UK). We recruited healthy individuals (n = 5) from the National Repository for Healthy Volunteers (NRHV) in Manchester. Two fresh 10-mL blood samples were collected from each participant following informed written consent and with ethical approval (from the National Research Ethics Service Committee North West – Haydock, Medical Research and Ethics Committee. Ref: 99/8/84) using ethylenediaminetetraacetic acid (EDTA) vacutainer collection tubes (BD Biosciences, UK). PBMCs were extracted using leucosep tubes (Greiner Bio-One, UK) and Ficoll-Paque Plus (Amersham Biosciences, UK). For each participant, one sample was prepared for fluorescence-activated cell sorting (FACs) fresh while the other was cryopreserved at −150°C (vapour phase of liquid nitrogen) for 1–3 months. CD3+CD4+ T cells were separated from each PBMC sample using a FACSAriaTM (BD Biosciences). The DNA methylation level in each sample was then measured using the HumanMethylation450 BeadChip according to the manufacturer’s guidelines (Illumina). After quality control of the samples in the minfi package in R (3), the samples were SWAN normalized (4) and probes that failed a detection p-value of 0.1 (n = 1424) or mapped to the X or Y chromosomes (n = 11 648) were removed, leaving 473 453 probes for analysis. Differentially methylated positions were identified using the CpGassoc package in R (5). Linear mixed models were used to detect probe level differences, controlling for multiple testing at the 5% false discovery rate (FDR) threshold. Beta values of methylation from each pair of samples (cryopreserved vs. fresh) within an individual were then compared using Pearson’s product-moment correlation. No probes were found to be differentially methylated with an FDR of 5%. All pairs of samples correlated with Pearson’s correlation values of 0.994 or above (Figure 1).
A STUDY OF BIRTH WEIGHT, PLACENTAL WEIGHT AND MORTALITY OF TWINS AS COMPARED TO SINGLETONS

A study was made of 1655 sets of twins born between 1931 and 1975 in two clinical centres. Compared to singletons, twins were born three weeks earlier, weighed less at birth from 33 weeks to term and had smaller placentae from 21 to 22 weeks to term. The influence on birth weight of sex was smaller in twins, the influence of parity greater. Because, compared to singletons, lower placental indices were found in twins up to 37 to 38 weeks, the conclusion is drawn that the retardation of growth in twins is to some extent due to the placenta itself. When singletons and twins of the same gestational age were compared, the mortality was found to be similar, somewhat lower in twins up to 37 to 38 weeks and higher afterwards. Monochorial twins were found to be born earlier, weigh less at birth and have a higher mortality than dichorial twins. Placental weights were not different and the conclusion is drawn that the retardation of growth in monochorial twins is to some extent due to the higher incidence of marginal and velamentous insertions of the umbilical cord associated with lower birth weights.
Mechanisms That Prevent Template Inactivation by HIV-1 Reverse Transcriptase RNase H Cleavages*

The RNase H activity of human immunodeficiency virus, type 1 (HIV-1) reverse transcriptase (RT) cleaves the viral genome concomitant with minus strand synthesis. We previously analyzed RT-mediated pausing and RNase H cleavage on a hairpin-containing RNA template system and reported that RT generated 3′ end-directed primary and secondary cuts while paused at the base of the hairpin during synthesis. Here, we report that all of the prominent cleavage products observed during primer extension on this template correlated with pause induced cuts. Products that persisted throughout the reaction corresponded to secondary cuts, about eight nucleotides in from the DNA primer terminus. This distance allows little overlap of intact template with the primer terminus. We considered whether secondary cuts could inactivate further synthesis by promoting dissociation of the primer from the template. As anticipated, 3′ end-directed secondary cuts decreased primer extendibility. This provides a plausible mechanism to explain the persistence of secondary cut products in our hairpin template system. Improving the efficiency of synthesis by increasing the concentration of dNTPs or addition of nucleocapsid protein (NC) reduced pausing and the generation of pause related secondary cuts on this template. Further studies reveal that 3′ end-directed primary and secondary cleavages were also generated when synthesis was stalled by the presence of 3′-azido-3′-deoxythymidine at the primer terminus, possibly contributing to 3′-azido-3′-deoxythymidine inhibition. Considered together, the data reveal a role for NC and other factors that enhance DNA synthesis in the prevention of RNase H cleavages that could be detrimental to viral replication.
A comprehensive study of polymorphisms in ABCB1, ABCC2 and ABCG2 and lung cancer chemotherapy response and prognosis

ATP‐binding cassette (ABC) transporter expression and genetic heterogeneity have been implicated in response to anticancer therapy. This study characterized genetic variability of the ABCB1 (also known as MDR1), ABCC2 (MRP2) and ABCG2 (BCRP) genes, which are key players in the metabolism of many chemotherapeutic agents including those used in the treatment of lung cancer. We genotyped 53 polymorphisms in the candidate genes in genomic DNA samples of 171 cases of small cell lung carcinoma (SCLC) and 206 cases of non‐small cell lung carcinoma (NSCLC), and studied their impact on early response to chemotherapy, progression‐free survival and overall survival. SNP rs717620 in ABCC2 was moderately associated with a poor response to chemotherapy but strongly with shorter progression‐free survival and overall survival in SCLC but not NSCLC patients, indicating that ABCC2 genetic variation is an important factor in SCLC survival after chemotherapy.
Comparison of cholesterol-lowering effect of β-glucan in cereals and bread

High levels of total- and LDL-cholesterol in blood are risk factors related to cardio-vascular disease. One of several measures to prevent this is consumption of the viscous soluble fibre β-glucan that in high amount is found in oats. In 2006, EFSA approved the health claim that a dose of at least 3 g β-glucan per day maintains normal blood cholesterol concentrations. The cholesterol-lowering properties of β-glucan have been shown to vary based on the processing and use in products. The aim of this literature review was to compare the cholesterol-lowering effect of oat β-glucan in ready-to-eat cereals and bread. These two products are easily accessible and common in the western diet. They can contain β-glucan of the same source but differ in several steps of manufacturing. The cholesterol lowering property of oat β-glucan is primarily affected by the solubility and molecular weight distribution. In bread making, fermentation and the use of flour with low falling number can decrease molecular weight and increase solubility. In the manufacturing extruded ready-to-eat cereals, high molecular weight is retained and solubility increased. One of the possible cholesterol lowering mechanisms of β-glucan is by increased hepatic bile acid production from choles-terol either endogenously synthesized or taken from the circulation. Six studies with ready-to-eat cereals and five studies with bread or muffins, cookies and buns were included for comparison. Eight out of the selected eleven studies reported a significant decrease in total- and LDL-cholesterol. Regarding dose of β-glucan and study subjects, the studies with cereals had more similarities and achieved more consistent results compared to the studies with bread. Ready-to-eat cereals seem to be a more favourable product than bread for oat β-glucan consumption in order to achieve a cholesterol reduction, due to more beneficial effects of processing on molecular weight and solubility of the β-glucan.
Dipeptides promote folding and peptide binding of MHC class I molecules

MHC class I molecules bind only those peptides with high affinity that conform to stringent length and sequence requirements. We have now investigated which peptides can aid the in vitro folding of class I molecules, and we find that the dipeptide glycyl-leucine efficiently supports the folding of HLA-A*02:01 and H-2Kb into a peptide-receptive conformation that rapidly binds high-affinity peptides. Treatment of cells with glycyl-leucine induces accumulation of peptide-receptive H-2Kb and HLA-A*02:01 at the surface of cells. Other dipeptides with a hydrophobic second amino acid show similar enhancement effects. Our data suggest that the dipeptides bind into the F pocket like the C-terminal amino acids of a high-affinity peptide.