Miracle-dz/UniFAR-FTUs huggingface dataset:
Cellular consequences of thrombin-receptor activation.

To say that thrombin is a multi-functional protein is rather to understate the case. It is the key enzyme involved in haemostasis, playing important roles at all levels of complexity. First, in the coagulation cascade, thrombin converts fibrinogen into fibrin, which is readily cross-linked to form a clot (reviewed in [1,2]) ; secondly, thrombin activates blood platelets, causing aggregation and secretion [3,4] ; and thirdly, thrombin can elicit mitogenic responses from vascular smooth-muscle cells [5,6]. This latter property is probably most significant in the renewal of damaged blood-vessel walls. Additionally, thrombin is able to elicit responses from cell types as diverse as macrophages [7], monocytes [8] and neutrophils [9]. Perhaps more surprisingly, it is able to regulate neurite outgrowth from cells of neuronal origin [10] and initiate resorption of bone cells [11]. All of these properties of thrombin appear to rely on its action as a serine proteinase, since modification (either chemically [12–14] or mutationally [15–17]) which destroys its proteolytic activity leads to a loss of biological activity. These crucial findings have been explained to a large extent by the recent elegant characterization of a novel, widely expressed thrombin receptor which is activated by proteolytic cleavage rather than by ligand (protein) binding [18,19]. At the same time as elucidation of the mechanism of thrombin signalling there has been a dramatic increase in our understanding of how thrombin signals are mediated within the cell. This therefore seems an appropriate time to assess our current knowledge and perhaps to try to predict areas where the greatest advances will be made in the immediate future. In this review, because of limitations in length, emphasis will be placed on recent advances, in particular on the characterization of the thrombin receptor and in the mechanisms of intracellular signalling. Whilst most studies of thrombin have concentrated on its action on cells involved in blood clotting and wound healing, it is now becoming apparent that it can modulate the growth and differentiation status of cells of neuronal origin. A consideration of recent advances in this area of study will form the third major theme of this review.
Resolution in time-frequency

We introduce a new measure H/sub p/ that is related to the Heisenberg uncertainty principle. The measure predicts the compactness of discrete-time signal descriptions in the sample-frequency phase plane. We conjecture a lower limit on the compaction in the phase plane and show that discretized Gaussians may not provide the most compact basis.
Parvovirus B19 viraemia in Dutch blood donors

Blood, donated by asymptomatic donors, may contain and transmit parvovirus B19. To investigate the dynamics of parvovirus viraemia in asymptomatic blood donors, we studied the amounts of parvovirus DNA in pools of donor plasma, the prevalence of parvovirus antibodies among blood donors in relation to age, and the seasonal and year-to-year variation of the incidence of parvovirus infection in The Netherlands. The incidence of parvovirus infection follows a seasonal cycle and a cycle of several years. Among Dutch blood donors the incidence was estimated to be 0·56% per year. Forty seven out of 100 pools of 5000 plasma donations tested positive for parvovirus DNA. We inferred that the course of viraemia in asymptomatic donors shows a short peak (>109 copies parvovirus DNA/ml), followed by viraemia below 106 copies/ml for about 2 weeks.
Nanotechnology and Regenerative Medicine Independent Passive Mechanical Behavior of Bovine Extraocular Muscle Compartments

METHODS. Putative compartments of each of the six whole bovine anatomical EOMs were separately clamped to a physiologically controlled, dual channel microtensile load cell (5-mN force resolution) driven by independent, high-speed, linear motors having 20-nm position resolution. One channel at a time was extended or retracted by 3 to 5 mm, with the other channel stationary. Fiducials distributed on the EOM global surface enabled optical tracking of local deformation. Loading rates of 5 to 100 mm/sec were applied to explore speeds from slow vergence to saccades. Control loadings employed transversely loaded EOM and isotropic latex.
Cumulative Increase in Serum Furosemide Concentration Following Repeated Doses in the Newborn

In order to test whether repeat doses of the diuretic furosemide result in plasma accumulation of this drug, eight newborns (mean birthweight, 1252 gm; mean gestational age, 27.5 weeks; mean postnatal age, 44.7 days; and normal renal function) were each given a 1-mg/kg iv bolus every 12 hr for four doses and maintained normally hydrated throughout the study period. Serum furosemide peak concentrations (1 hr after administration) were measured in eight newborns, and trough levels in four newborns, by HPLC. The mean 1-hr serum furosemide level increased with repeated doses of the drug, from 3.18 +/- 0.52 to 7.95 +/- 2.36 mg/liter (mean +/- SE) (p less than .05). In contrast, the mean serum trough concentration of furosemide remained at a plateau following the first dose (1.8 +/- 0.82 to 1.98 +/- 1.81 mg/liter), suggesting attainment of a steady state. This accumulation of furosemide following repeated doses of this diuretic, therefore, reflects the decreased plasma clearance of the drug, possibly due to contraction of its volume of distribution.
All in the family: social processes in ovarian egg donation between sisters.

Interviews and participant observation were conducted at a US infertility clinic with women who were attempting to become pregnant with eggs donated by their biological sisters. Sisters who donated eggs were also followed and interviewed regarding their experiences, as were a number of husbands of recipients. Five significant social processes characterising the sisters’ passage through egg donation are discussed: (1) negotiating dissimilar treatment experiences, (2) communicating cautiously, (3) interacting in a triad, (4) disclosing to others, and (5) ‘gift-giving’. Although participants are generally satisfied with their decision to do sister-to-sister egg donation, the unprecedented procedure presents a number of difficulties. If sister-to-sister egg donation as a means to biological motherhood continues in the future, these sociological findings suggest areas in which medical personnel may need to provide social and emotional support.
Coexistence of leishmaniasis and multiple myeloma in the era of monoclonal antibody (anti-CD38 or anti-SLAMF7) containing triplets: one shared story of two exceptional cases

Multiple myeloma (MM) patients are considered severely immune-compromised and at high risk of opportunistic infections, independently of the therapeutic approach and the response status. Leishmaniasis seems to behave as such an opportunistic infection; the incubation time of initial infection ranges between 2 and 6 months, while a recurrence of latent infection is possible [1]. It is a rare vector-borne infection that is caused by more than 20 species of an intramacrophage protozoon, which is transmitted to humans by more than 30 different species of phlebotomus sandflies (or less often by contaminated blood products transfusion) [1–3]. Although leishmaniasis is an endemic disease with 90% of cases occurring in tropical and subtropical areas (e.g. Brazil, India but also South and Mediterranean Europe) [2,4], more recently with the growth of international travel, its frequency is also increasing in western countries. This predominantly occurs in immune-compromised patients, including patients with HIV-acquired immunodeficiency [5,6], patients who underwent an organ or hematopoietic stem cell transplantation [4,7–11] and patients with lymphoproliferative disorders who were treated with anti-CD52 and anti-CD20 monoclonal antibodies [12,13]. Recent epidemiological data have shown that novel antimyeloma agents and their combinations have contributed significantly to the increased risk of conventional bacterial and viral infections in MM patients observed in the last decades [14]. However, limited data are available on the incidence of opportunistic fungal and parasitic infections in MM patients who are treated with novel agents. Currently, the approval of monoclonal antibodies (mAbs)-containing triplets, including daratumumab (a human IgGj mAb-targeting surface protein CD38) or elotuzumab (a humanized G1 mAb-targeting surface glycoprotein SLAMF7) in combination with lenalidomide and dexamethasone for relapsed MM has increased the therapeutic options for myeloma patients and has intensified the immune-mediated management [15,16]. In this letter, we present two ‘real-world’ MM patients who developed leishmania infection, which recurred during antimyeloma treatment with a triplet of a mAb with lenalidomide and dexamethasone. In addition, we describe our therapeutic decisions for both diseases and our considerations about the interaction of mAb-triplets and the immune background of underlying leishmania infection.
Evaluation of the Immunogenicity and Vaccine Potential of Recombinant Plasmodium falciparum Merozoite Surface Protein 8

ABSTRACT The C-terminal 19-kDa domain of merozoite surface protein 1 (MSP119) is the target of protective antibodies but alone is poorly immunogenic. Previously, using the Plasmodium yoelii murine model, we fused P. yoelii MSP119 (PyMSP119) with full-length P. yoelii merozoite surface protein 8 (MSP8). Upon immunization, the MSP8-restricted T cell response provided help for the production of high and sustained levels of protective PyMSP119- and PyMSP8-specific antibodies. Here, we assessed the vaccine potential of MSP8 of the human malaria parasite, Plasmodium falciparum. Distinct from PyMSP8, P. falciparum MSP8 (PfMSP8) contains an N-terminal asparagine and aspartic acid (Asn/Asp)-rich domain whose function is unknown. Comparative analysis of recombinant full-length PfMSP8 and a truncated version devoid of the Asn/Asp-rich domain, PfMSP8(ΔAsn/Asp), showed that both proteins were immunogenic for T cells and B cells. All T cell epitopes utilized mapped within rPfMSP8(ΔAsn/Asp). The dominant B cell epitopes were conformational and common to both rPfMSP8 and rPfMSP8(ΔAsn/Asp). Analysis of native PfMSP8 expression revealed that PfMSP8 is present intracellularly in late schizonts and merozoites. Following invasion, PfMSP8 is found distributed on the surface of ring- and trophozoite-stage parasites. Consistent with a low and/or transient expression of PfMSP8 on the surface of merozoites, PfMSP8-specific rabbit IgG did not inhibit the in vitro growth of P. falciparum blood-stage parasites. These studies suggest that the further development of PfMSP8 as a malaria vaccine component should focus on the use of PfMSP8(ΔAsn/Asp) and its conserved, immunogenic T cell epitopes as a fusion partner for protective domains of poor immunogens, including PfMSP119.
Development of the cerebellar afferent system in the shark Scyliorhinus canicula: Insights into the basal organization of precerebellar nuclei in gnathostomes

The cerebellum is recognized as an evolutionary innovation of jawed vertebrates, whose most primitive group is represented by the chondrichthyans, or cartilaginous fishes. A comprehensive knowledge of cerebellar connections in these fishes might shed light on the basal organization of the cerebellar system. Although the organization of the precerebellar system is known in adults, developmental studies are essential for understanding the origin and evolution of precerebellar nuclei. In the present work we performed a developmental study of cerebellar connections in embryos and juveniles of an advanced shark species, Scyliorhinus canicula, by application of tract tracing in combination with immunohistochemical techniques. Main precerebellar cell populations were located in the diencephalon (pretectum and thalamus), mesencephalon (reticular formation and nucleus ruber), rhombencephalon (cerebellar nucleus, reticular formation, and inferior olive), and spinal cord (ventral horn). The order of arrival of cerebellar afferent projections throughout development revealed a common pattern with other jawed vertebrates, which was helpful for comparison of stages of cerebellar development. The neurochemical study of the inferior olive and other precerebellar nuclei revealed many shared features with other gnathostomes. Furthermore, because many precerebellar nuclei originate from rhombic lips, the first analysis of neuronal migrations from these lips was performed with markers of neuroblasts. The shared features of development and organization of precerebellar connections observed between sharks and amniotes suggest that their basic pattern was established early in gnathostome evolution. J. Comp. Neurol. 522:131–168, 2014. © 2013 Wiley Periodicals, Inc.
Reducing Infusion Phlebitis in Singapore Hospitals Using Extended Life End-Line Filters

Two studies were conducted to investigate the impact of the 4-day end-line filter used to treat infusion phlebitis in Singapore. In the first study, conducted in 1997, 200 patients received IV antibiotics and chemotherapy. In the first 100 patients, end-line filters were not used during the infusions. This resulted in a phlebitis rate of 31%. In the second group of 100 patients, end-line filtration was used, resulting in a phlebitis rate of 5%. In 2000, a second study was conducted, measuring the outcome of end-line filtration versus no end-line filtration use. In this case, phlebitis developed in 35% of 100 patients receiving antibiotics, as compared with 8% of 394 patients with the use of 4-day end-line filtration. These are the first such studies performed in Southeast Asia that highlight identical benefits, namely the reduction of phlebitis by elimination of particulates, in two separate patient populations. End-line filtration, when used to deliver antibiotics and chemotherapy, will result in significantly fewer cases of infusion phlebitis, reduce the cost of delivering IV antibiotics and chemotherapy, increase nursing efficiency, and ultimately improve patient comfort.
The cytoplasmic tail of influenza A virus neuraminidase (NA) affects NA incorporation into virions, virion morphology, and virulence in mice but is not essential for virus replication

In this study, we investigated the role of the conserved neuraminidase (NA) cytoplasmic tail residues in influenza virus replication. Mutants of influenza A virus (A/WSN/33 [H1N1]) with deletions of the NA cytoplasmic tail region were generated by reverse genetics. The resulting viruses, designated NOTAIL, contain only the initiating methionine of the conserved six amino-terminal residues. The mutant viruses grew much less readily and produced smaller plaques than did the wild-type virus. Despite similar levels of NA cell surface expression by the NOTAIL mutants and wild-type virus, incorporation of mutant NA molecules into virions was decreased by 86%. This reduction resulted in less NA activity per virion, leading to the formation of large aggregates of progeny mutant virions on the surface of infected cells. A NOTAIL virus containing an additional mutation (Ser-12 to Pro) in the transmembrane domain incorporated three times more NA molecules into virions than did the NOTAIL parent but approximately half of the amount incorporated by the wild-type virus. However, aggregation of the progeny virions still occurred at the cell surface. All NOTAIL viruses were attenuated in mice. We conclude that the cytoplasmic tail of NA is not absolutely essential for virus replication but exerts important effects on the incorporation of NA into virions and thus on the aggregation and virulence of progeny virus. In addition, the relative abundance of long filamentous particles formed by the NOTAIL mutants, compared with the largely spherical wild-type particles, indicates a role for the NA cytoplasmic tail in virion morphogenesis.
Cryptic introgression into the kidney saxifrage (Saxifraga hirsuta) from its more abundant sympatric congener Saxifraga spathularis, and the potential risk of genetic assimilation.

BACKGROUND AND AIMS Although hybridization can play a positive role in plant evolution, it has been shown that excessive unidirectional hybridization can result in replacement of a species' gene pool, and even the extinction of rare species via genetic assimilation. This study examines levels of introgression between the common Saxifraga spathularis and its rarer congener S. hirsuta, which have been observed to hybridize in the wild where they occur sympatrically. METHODS Seven species-specific single nucleotide polymorphisms (SNPs) were analysed in 1025 plants representing both species and their hybrid, S. × polita, from 29 sites across their ranges in Ireland. In addition, species distribution modelling was carried out to determine whether the relative abundance of the two parental species is likely to change under future climate scenarios. KEY RESULTS Saxifraga spathularis individuals tended to be genetically pure, exhibiting little or no introgression from S. hirsuta, but significant levels of introgression of S. spathularis alleles into S. hirsuta were observed, indicating that populations exhibiting S. hirsuta morphology are more like a hybrid swarm, consisting of backcrosses and F2s. Populations of the hybrid, S. × polita, were generally comprised of F1s or F2s, with some evidence of backcrossing. Species distribution modelling under projected future climate scenarios indicated an increase in suitable habitats for both parental species. CONCLUSIONS Levels of introgression observed in this study in both S. spathularis and S. hirsuta would appear to be correlated with the relative abundance of the species. Significant introgression of S. spathularis alleles was detected in the majority of the S. hirsuta populations analysed and, consequently, ongoing introgression would appear to represent a threat to the genetic integrity of S. hirsuta, particularly in areas where the species exists sympatrically with its congener and where it is greatly outnumbered.
Long short-term memory based on a reward/punishment strategy for recurrent neural networks

Recurrent neural networks and their variants have received huge success in many difficult tasks, such as handwriting recognition and generation, natural language processing, acoustic modeling of speech, and so on. As a kind of recurrent neural network architectures, the long short-term memory (LSTM) has attracted great attention. Most research works focus on its structures, training algorithms and topology structures. As an improvement to the structure of LSTM, a reward/punishment strategy is developed for LSTM in this paper, which we call RP-LSTM. In RP-LSTM, a reward/punishment (RP) strategy is proposed to evaluate its memory cells' memorization such that it improves its efficiency by forgetting more reasonably. Analysis of properties of the developed RP-LSTM is conducted from the neuroscience aspect. To test the performance of the developed RP-LSTM, comparative simulation studies are conducted on three structures, i.e., LSTM, LSTM with forget gate (LSTM-FG) and RP-LSTM. Simulation results on sentiment analysis model and sequence to sequence model demonstrate that RP-LSTM achieves better performance.
Studies correlating the growth rate of a tumor and its metastases and providing evidence for tumor-related systemic growth-retarding factors.

Summary Previous studies have shown that the growth of a solid tumor is characterized by progressive slowing of the rate of growth as the tumor increases in size, but it is not clear to what extent local or systemic factors determine this slowing of growth rate. In this study, the growth of an implanted, isologous Lewis lung carcinoma in C57BL/6 mice was followed by serial tumor diameter measurements, and the number of tumor cells which had metastasized to lungs and kidneys was followed by serial quantitative transplant bioassay. Tumor diameter data were converted to tumor weight by a previously derived formula. Synchronous slowing of the rate of growth of the implanted tumor and its metastases was observed. Early after transplantation, the implanted tumor grew exponentially, and early lung metastases grew exponentially at a similar rate. Later, as the growth rate of the large implanted tumor slowed, a similar degree of slowing of the growth rate of metastases in lung and kidney was observed, even though these metastatic foci were microscopic in size. Host immunological factors did not seem to be involved, since challenge of animals at various stages of tumor growth with graded doses of tumor cells showed no evidence of transplantation resistance. Synchronous slowing of tumor growth rate was also demonstrated in experiments in which metastases were simulated by a 2nd implant. Following removal of the primary tumor, this slowing of tumor growth was reversible in both the lung metastases and the simulated metastases. These studies point to the importance of nonimmunological systemic factors (nutritional deficiencies or tumor by-products) that influence tumor growth rate.
Color Changes in Elasmobranchs.

Introduction. -The early work on the color changes in fishes was done exclusively on teleosts. The study of the chromatophoral activities in elasmobranchs dates back only a little over a decade. In 1921 Schaefer stated that Raja clavata and R. batis showed no alterations in tint when on white or on black backgrounds nor to faradic stimulation of the skin. Six years later, however, Weidenreich (1927) called attention to the remarkable circumstance that Raja oxyrhyncha when first taken from the sea had a light ventral surface, but after a day in an aquarium this surface became uniformly dark. By microscopic inspection it could be seen that in the light phase the melanophore pigment was concentrated, but that in the dark one it was dispersed. In 1933 I showed that of two specimens of Raja erinacea the one that was placed in an illuminated white-walled aquarium for eighteen hours became light brown and the other in a black-walled illuminated tank dark brown. On transferring each fish to the other tank the light fish became decidedly dark after nine hours in the black-walled tank and the dark one pinkish white after twelve hours in the whitewalled receptacle. From these last two sets of records it is clear that color changes occur in at least some species of rays. Meanwhile Lundstrom and Bard (1932) had demonstrated a striking change of tint in the dogfish, Mustelus.canis, and had shown that the dark phase of this fish was induced by secretions from the pituitary organ. Its light phase was subsequently declared by Parker and Porter (1934) to be dependent, upon nerves. The blanching of the skin in Mustelus could be induced not only through stimulating the concentrating melanophoral nerves by cutting them, but also by faradic stimulation (Parker, 1935a). It also appeared from subsequent work that the terminals of the melanophoral nerves excite the concentration of pigment in the integumentary color cells through the production of an oil-soluble neurohumor, a lipohumor (Parker, 1935b). These investigations were carried on without knowledge of the work done by Young (1933) on the autonomic nervous system in elasmobranchs. After a very exhaustive study of this part of the selachian nervous system, Young was able to show, particularly in Scyllium, that there were no recurrent gray remi communicantes, connections over which the autonomic nerve-fibres to the chromatophores regularly pass. Moreover, section of spinal, trigeminal or facial nerves was followed by no color changes in the skin nor did the skin blanch to injections of adrenalin. Fragments of skin VOL. 22, 1936 55