Miracle-dz/UniFAR-FTUs huggingface dataset:
Sequential docking, molecular differentiation, and positioning of T-Tubule/SR junctions in developing mouse skeletal muscle.

Skeletal muscle Ca(2+) release units (CRUs) are junctions of the surface membrane/T-tubule system and the sarcoplasmic reticulum (SR) that function in excitation-contraction coupling. They contain high concentrations of dihydropyridine receptors (DHPRs) in the T-tubules and of ryanodine receptors (RyR) in the SR and they are positioned at specific locations in the sarcomere. In order to characterize the sequence of developmental steps leading to the specific molecular and structural organization of CRUs, we applied a range of imaging techniques that allowed us to follow the differentiation of the membrane compartments and the expression of junctional proteins in developing mouse diaphragm muscle. We find that docking of the two membrane systems precedes the incorporation of the RyRs into the junctions, and that T-tubule/SR junctions are formed and positioned at the I-A interface at a stage when the orientation of T-tubule is predominantly longitudinal. Thus, the sequence of developmental events is first the docking of T-tubules and SR, secondly the incorporation of RyR in the junctions, thirdly the positioning of the junctions in the sarcomere, and only much later the transverse orientation of the T-tubules. These sequential stages suggests an order of inductive processes for the molecular differentiation and structural organization of the CRUs in skeletal muscle development.
Use of Immunosuppressants and Biologicals in Patients with Previous Cancer

Thiopurines promote Epstein-Barr virus-related lymphomas, nonmelanoma skin cancers and acute myeloid leukemias. Anti-tumor necrosis factor (anti-TNF) agents may inhibit or activate carcinogenesis according to the cellular pathways that are activated. A mild increase in the risk of melanoma has been reported in patients exposed to anti-TNF agents. Transplanted patients with previous history of cancer are at high risk of cancer recurrence when receiving posttransplant immunosuppressive therapy, particularly within the first 2 years of treatment. Few data exist for patients with chronic inflammatory disease. In the CESAME cohort that included essentially patients receiving thiopurines, there was no excess incidence of recurrent or new cancer associated with exposure to immunosuppressive therapy in the patients with previous cancer at cohort entry. In clinical practice, the decision to start or resume immunosuppressive therapy in inflammatory bowel disease (IBD) patients with recent cancer should be discussed case by case with cancer specialists. However, taken into account the experience of transplant specialists, it could be suggested not to consider a waiting period for women with adequately treated uterine high-grade cervical dysplasia. For invasive cancers, a waiting period of 2 years should be considered if possible. During this period, treatment of IBD should be restricted to 5-aminosalicylic acid, steroids, nutritional therapy, or surgery, except in case of aggressive IBD that cannot be controlled by these methods. A longer waiting period of 5 years could be recommended for the most aggressive forms of cancers, such as melanomas, aggressive breast cancers, sarcomas, urinary tract cancers, and myelomas.
Atherosclerosis: cell biology and lipoproteins.

DOI:10.1097/MOL.0b013e32835c7bb7 Atherosclerosis-based cardiovascular diseases have a devastating impact on public health. Therefore, exploring molecular mechanisms of atherosclerosis is an important focus for development of effective therapeutic strategies [1]. This Bimonthly Update summarizes recent publications that have provided new insights into leukocyte-related mechanisms in the development of atherosclerosis. Macrophage accumulation is a dominant feature of early atherosclerosis and could be due to changes in recruitment, emigration, proliferation, or death. To gain insights into mechanisms provoking macrophage emigration, van Gils et al. [2 && ] investigated netrin-1, a protein involved in chemorepulsion and chemoattraction of axons. Netrin-1 was present in macrophages of atherosclerotic lesions. Several in-vitro studies were consistent with this protein being an active participant in the atherosclerotic process including lipid loading of cultured macrophages increasing the abundance of netrin-1. Netrin-1 also inhibited macrophage migration by preventing responses to a number of chemokines. In addition, netrin-1 expression in macrophages was a chemoattractant for smooth muscle cells. Supported by these in-vitro data, the authors performed in-vivo studies demonstrating that netrin-1 deficiency in hematopoietic cells reduced hypercholesterolemia-induced atherosclerosis in LDL receptor / mice. A macrophagetracking technique provided evidence that netrin-1 deficiency in hematopoietic cells led to less retention of macrophages in atherosclerotic lesions. Despite not being directly demonstrated, these data inferred that inhibition of netrin-1 might be able to remove lipid-laden macrophages from established atherosclerotic lesions. The effects of netrin-1 in atherosclerosis have been explored previously. In contrast to the studies of van Gils et al. [2 && ], others reported that netrin-1 delivered via infection with adeno-associated viruses prevented atherosclerosis by reducing leukocyte accumulation [3 & ]. Part of the contradiction may be the result of the unusual approach used by Khan et al. [3 & ] to measuring atherosclerosis. However, there may also be a context-based explanation because netrin-1 inhibits migration of circulating leukocytes into tissues, thereby it may exert anti-inflammatory
Value Creation in Innovation Ecosystems: How the Structure of Technological Interdependence Affects Firm Performance in New Technology Generations

The success of an innovating firm often depends on the efforts of other innovators in its environment. How do the challenges faced by external innovators affect the focal firm's outcomes? To address this question we first characterize the external environment according to the structure of interdependence. We follow the flow of inputs and outputs in the ecosystem to distinguish between upstream components that are bundled by the focal firm, and downstream complements that are bundled by the firm's customers. We hypothesize that the effects of external innovation challenges depend not only on their magnitude, but also on their location in the ecosystem relative to the focal firm. We identify a key asymmetry that results from the location of challenges relative to a focal firm—greater upstream innovation challenges in components enhance the benefits that accrue to technology leaders, while greater downstream innovation challenges in complements erode these benefits. We further propose that the effectiveness of vertical integration as a strategy to manage ecosystem interdependence increases over the course of the technology life cycle. We explore these arguments in the context of the global semiconductor lithography equipment industry from its emergence in 1962 to 2005 across nine distinct technology generations. We find strong empirical support for our framework. Copyright © 2009 John Wiley & Sons, Ltd.
Les verbes causatifs polymorphiques : Les prédicats complexes en français

A. Zaenen & M. Dalrymple : ; The syntactic analysis of French causative constructions relies on the distinction, crucial in the LFG formalism, between the constituent structure (hierarchical : faire takes a VP complement) and the functional structure (flat : faire and the infinitival V form a complex predicate in a unique functional structure). The semantic representation is constructed from the f-structure, lexical semantic information (which specifies ; semantic roles associated with each predicate), and independent rules which map functions onto semantic roles. This construction takes the general form of a deduction in linear logic, whose property of resource sensitivity is exploited to give the effect of completeness and coherence, which are general constraints on linguistic structures.
Allergy and risk of glioma: a meta‐analysis

We evaluated the association between allergic conditions and the risk of glioma in case–control and cohort studies published so far on this issue. A total of 12 studies (10 case–control and 2 cohort studies) were included in the analysis, involving 61 090 participants, of whom 6408 had glioma. When compared with non‐allergic conditions, the pooled odds ratio (OR) with any allergic conditions for glioma was 0.60 (95% CI: 0.52–0.69, P < 0.001), suggesting a significant negative association (protective effect) between allergy and glioma. Subgroup analysis showed that the ORs were 0.70 (95% CI: 0.62–0.79, P < 0.001), 0.69 (95% CI: 0.62–0.78, P < 0.001), and 0.78 (95% CI: 0.70–0.87, P < 0.001) for asthma, eczema, and hay fever, respectively. The significant association remained even after excluding the bias of proxy reporting (OR = 0.61; 95% CI: 0.50–0.75, P < 0.001). We conclude that allergic conditions may significantly reduce the risk of glioma.
Influence of Temperature on the Steady State and Transient Luminance of an OLED Display

In this paper, the influence of temperature on the luminance of an organic light-emitting device (OLED) display is investigated. Luminance, temperature, and power measurements are executed on a 55-in white-red-green-blue active-matrix OLED display with a resolution of 1920 × 1080 and an oxide-thin-film-transistor (TFT) backplane, under a controlled, static temperature environment. The measurements indicate a strong influence of temperature on the luminance of the display, resulting from the temperature dependence of both the TFT and the OLED. The influence of temperature on the luminance of an OLED display is also investigated in a dynamic context. Measurements show that temperature changes resulting from losses in the display have an important influence on the luminance stability of the display. The measurements linking luminance and temperature in a static temperature environment allow estimating the change in luminance in a dynamic context. Finally, this paper presents the results of a number of experiments that were set up to show scenarios in which the temperature dependence of the display's luminance has a direct negative impact on the picture quality of the display. The results of this work show that the thermal behavior of an OLED display must be taken into account when working towards a high-performing OLED display.
Scaphocephaly Part II: Secondary Coronal Synostosis After Scaphocephalic Surgical Correction

Aim: Occurrence of secondary coronal synostosis (SCS) and its functional consequences were retrospectively analyzed in sagittal synostosis. Patients and Methods: Occurrence of SCS and/or fingerprinting and clinical signs of raised intracranial pressure were investigated in children with scaphocephaly with a minimum follow-up of 3 years. Children were divided in 4 groups according to surgery (group 1: "H" craniectomy [193 patients]; group 2: craniectomies with removal of the coronal sutures [24 children]; group 3:"H" craniectomies and flap transpositions without total removal of the coronal suture [36 patients]; and group 4: 253 nonsurgical patients with scaphocephaly). Results: Among group 1, 20 (10.4%) developed SCS (3 mo to 6 y postoperatively). Fingerprinting was generalized in 13 patients, localized in 5, and absent in 2. Headaches were present in 8 patients. Papilledema appeared during follow-up in 2 of them. Intracranial pressure that was first recorded as normal became elevated, and they both required a surgical decompression. In group 2, none developed an SCS. In group 3, 11% developed SCS. In group 4, 1.2% nonsurgical patients with scaphocephaly presented with an SCS. However, group 4 corresponds to less severe morphologic deformation and/or parents refusing surgery. Conclusions: Secondary coronal synostosis appears to occur with an approximate 10% incidence after craniectomies not involving the coronal sutures, with 1% requiring surgical decompression. Patients with milder forms of scaphocephaly who were not operated on (1.2%) rarely developed an SCS. Long-term follow-up should be undertaken even in the milder forms for possible recurrence of secondary synostosis.
Growth, Nutrient Utilization and Amino Acid Digestibility of Dairy Calves Fed Milk Replacers Containing Different Amounts of Protein in the Preruminant Period

This study was designed to examine the effects of different dietary protein levels on growth performance, nutrient utilization, amino acid (AA) digestibility and serum biochemical parameters of preruminant dairy calves. Fifteen healthy new-born calves were randomly allotted to three experimental groups and fed with different milk replacer that contained 18% (LP), 22% (MP) or 26% (HP) of protein. The results showed that final BW, net gain and ADG were significantly higher in the MP group than in LP and HP groups (p 0.05). BUN concentration, on the other hand, decreased as calves grew but increased following the increase of dietary CP content. Furthermore, no significant differences in digestibility of amino acids were observed among these three groups of animals (p>0.05). We concluded that calves fed with milk replacer containing 22% of protein had better growth performance and nutrient utilization as compared to animals treated with milk replacer containing either 18% or 26% of protein.
The effects of geometry on skin penetration and failure of polymer microneedles

Microneedles are small-scale devices that may be used for drug delivery and biosensing. In this study, the forces required for mechanical failure, the modes of mechanical failure, as well as the mechanisms for microneedle penetration into porcine skin were examined. Microneedles produced from the acrylate-based polymer e-Shell 200 using an indirect rapid prototyping approach involving two-photon polymerization and poly(dimethylsiloxane) micromolding were found to possess sufficient strength for penetration of porcine skin. The failure forces were an order of magnitude greater than the forces necessary for full insertion into the skin. Bending was the most common form of failure; an increasing aspect ratio and a decreasing tip diameter were associated with lower failure forces. Video captured during skin penetration revealed that microneedle penetration into the skin occurred by means of a series of insertions and not by means of a single insertion event. Images obtained during and after skin penetration confirmed microneedle penetration of skin as well as transdermal delivery of lucifer yellow dye. These findings shed insight into the mechanisms of microneedle penetration and failure, facilitating design improvements for polymer microneedles.
Optical coherence tomography as a biomarker in multiple sclerosis.

INTRODUCTION Multiple sclerosis (MS) is a disease of the central nervous system (CNS) that leads to axonal dysfunction and neuronal loss and often presents optic neuritis (ON). Decreased thickness of the retinal nerve fiber layer (RNFL) is a classic finding on ophthalmoscopic examination of patients with MS and especially noted in those patients with a history of ON. The thickness of the RNFL can be measured by a non-invasive technique, optical coherence tomography (OCT). AREAS COVERED This review will cover the history and development of the OCT technology and the advantages of a potential clinical application as a biomarker for axonal loss in MS. EXPERT OPINION The use of OCT to quantify axonal loss in the RNFL is a promising tool to evaluate disease progression in MS and ON patients. OCT measurements may also correlate with MRI measured brain atrophy and could provide an easily quantified and highly reproducible method in clinical trials to monitor the efficacy of both immune- and neuroprotective therapies. Potential correlations between OCT with other biomarkers that include low contrast vision, visual evoked potentials, color vision and diffusion tensor imaging of the brain and advanced imaging of the optic nerve are promising new frontiers of research.
Granulocyte colony‐stimulating factor (G‐CSF) receptors on acute myeloblasts leukaemia cells and their relationship with the proliferative response to G‐CSF in clonogenic assay

Summary. The number and the affinity of granulocyte colony‐stimulating factor (G‐CSF) receptors expressed by blast cells in acute myeloblastic leukaemia (AML) were determined using radiolabeled recombinant human G‐CSF (rhG‐CSF). Eighteen of 20 patients demonstrated specific binding, and Scatchard analysis revealed a single class of high affinity (Kd 15‐130 pM) G‐CSF receptors on the AML blasts. The number of G‐CSF receptors varied from 55 to 1200 per cell (mean 278). In the remaining two patients, specific binding was not observed. The number of G‐CSF receptors did not differ significantly between various AML subtypes, but the mean receptor number was the highest on type M2 blasts. A chemical cross‐linking study revealed that the G‐CSF receptor has an approximate molecular weight of 140 000. Autoradiography showed heterogeneity of the distribution of G‐CSF receptors on the AML blasts obtained from a single patient. The number of colonies stimulated by the addition of rhG‐CSF varied from 0 to 566 per dish, and blast colony formation was observed in eight of 20 patients. The population mean of G‐CSF receptor number expressed by blasts that formed colonies on stimulation with rhG‐CSF was significantly higher than that on blasts which did not form colonies. These results suggest that a proliferative response of AML blasts to G‐CSF may be predicted when the blasts express a large number of G‐CSF receptors. Accordingly, it may be safer to restrict the clinical use of G‐CSF to AML patients who have blasts with a low G‐CSF receptor expression and no response to G‐CSF in blast colony assay.
Immunomodulators in the treatment of cutaneous lymphomas

Cutaneous lymphomas (CLs) are a heterogeneous group of lymphoproliferative cutaneous neoplasms that in many cases cannot be cured by standard radio- and chemotherapy. Immunotherapy holds promise for a well tolerated treatment approach that allows long-time disease control. Unspecific immunotherapy such as IFNs are successfully used in cutaneous T-cell lymphomas (CTCLs). Antibiotic treatment is often effective in cutaneous B-cell lymphomas (CBCLs). New treatment approaches include fusion toxins and chimeric monoclonal antibodies (mAbs) such as rituximab for CBCLs. The identification of tumour antigens in CTCLs renders these diseases susceptible for vaccination approaches.
Scientific Realism and Invariance

In this paper, I will be concerned with the realist/anti-realist issue in the context of science, and I will be defending some version of scientific realism. The discussion will be conducted at the epistemological, and not the metaphysical, level. I will start from Kant's definition of reality as "that which is connected with perception according to laws" quoted by Hermann Weyl in his Philosophy of Mathematics and Natural Science (1963, p. 122). 1 Of course, the concepts of perception and law are at least as entangled as the notion of reality and Kant's definition, as it stands, is open to a wide variety of interpretations. I do not want here to enter in such a discussion, let alone in an exegetic debate about the meaning of reality in Kant's thought.
An APAF-1·Cytochrome c Multimeric Complex Is a Functional Apoptosome That Activates Procaspase-9*

We report here the reconstitution of the de novo procaspase-9 activation pathway using highly purified cytochrome c, recombinant APAF-1, and recombinant procaspase-9. APAF-1 binds and hydrolyzes ATP or dATP to ADP or dADP, respectively. The hydrolysis of ATP/dATP and the binding of cytochromec promote APAF-1 oligomerization, forming a large multimeric APAF-1·cytochrome c complex. Such a complex can be isolated using gel filtration chromatography and is by itself sufficient to recruit and activate procaspase-9. The stoichiometric ratio of procaspase-9 to APAF-1 is approximately 1 to 1 in the complex. Once activated, caspase-9 disassociates from the complex and becomes available to cleave and activate downstream caspases such as caspase-3.
Como é possível vivermos e convivermos em um mundo real e nos comunicarmos exclusivamente no âmbito de um universo discursivo

O fenomeno da deixis tem merecido pouca atencao dos estudos linguisticos. Nao ede se estranhar que assim seja, uma vez que a nocao de deixis esta atrelada a propria nocaode lingua e admitir a existencia da deixis implica rejeitar as nocoes de sistema linguisticoabstrato ou de universo discursivo, ambos separados do mundo ambiental, conforme sepostula. A questao que discutimos aqui e: Como e possivel vivermos e convivermos em ummundo real, e nos comunicarmos atraves de um sistema linguistico abstrato ou no âmbitode um universo discursivo? Respaldados em estudos sobre a linguagem humana de baseevolucionista e cognitivista, nossa proposta e apresentar evidencias de que nos comunicamosem um mundo real e de que a deixis constitui um elo entre o mundo ambiental e a gramaticade uma lingua.
PRESTO: A system for object‐oriented parallel programming

PRESTO is a programming system for writing object‐oriented parallel programs in a multiprocessor environment. PRESTO provides the programmer with a set of pre‐defined object types that simplify the construction of parallel programs. Examples of PRESTO objects are threads, which provide fine‐grained control over a program's execution, and synchronization objects, which allow simultaneously executing threads to co‐ordinate their activities.
Resetting of the cardiopulmonary baroreflex 10 years after surgical repair of coarctation of the aorta

OBJECTIVE To characterise cardiopulmonary baroreflex responses and examine the effects of a 45 minute cycling bout late after successful repair of coarctation of the aorta. SUBJECTS 10 young adults (mean (SEM) age 18.1 (2.6 years)) operated on for coarctation of the aorta 12.7 (3.5) years earlier, and 10 healthy controls. DESIGN Forearm blood flow (venous occlusion plethysmography) and vascular resistance, left ventricular internal diastolic diameter, and central venous pressure estimated from an antecubital vein were measured in the supine position at baseline and during five minute applications of lower body negative pressure (LBNP) at −15 mm Hg (LBNP−15) and −40 mm Hg (LBNP−40). Venous samples were obtained at baseline and during LBNP−40 for noradrenaline (norepinephrine), adrenaline (epinephrine), renin activity, and aldosterone. The tests were repeated after 45 minutes of moderate exercise. RESULTS Baseline heart rate (78 (9)v 64 (6) beats/min), echocardiographic cardiac output (6.9 (1.1) v 5.0 (0.2) l/min), shortening fraction (41.7 (1.8)% v 33.3 (1.3)%), and forearm blood flow (3.4 (0.4) v2.3 (0.3) ml/100 g/min) were higher in the coarctation group than in the controls (p < 0.05). Changes in forearm blood flow and forearm vascular resistance from baseline to LBNP−40 were similar in both groups, but the relation between forearm vascular resistance and estimated central venous pressure or left ventricular internal diastolic diameter was shifted downward in the coarctation group. Plasma adrenaline was increased in the coarctation group (baseline: 3.2 (0.6) v 2.4 (0.3) pmol/l in controls; LBNP−40: 687 (151) v 332 (42) pmol/l) (p < 0.05). Both groups showed a similar downward displacement of forearm vascular resistance (p < 0.05) after exercise. CONCLUSIONS There appears to be resetting of the cardiopulmonary baroreflex to a lower forearm vascular resistance in young adults operated on for coarctation of the aorta, associated with hyperdynamic left ventricular function. Raised circulating adrenaline could contribute to the lower forearm vascular resistance.
Chikungunya Virus, Southeastern France

In September 2010, autochthonous transmission of chikungunya virus was recorded in southeastern France, where the Aedes albopictus mosquito vector is present. Sequence analysis of the viral genomes of imported and autochthonous isolates indicated new features for the potential emergence and spread of the virus in Europe.