Miracle-dz/UniFAR-FTUs huggingface dataset:
Transcriptional regulation of the human interleukin 1beta gene by fibronectin: role of protein kinase C and activator protein 1 (AP-1).

Interleukin 1beta (IL-1beta) is a multifunctional polypeptide considered a key cytokine during inflammation. Fibronectin (FN), a matrix glycoprotein highly expressed in injured tissues, can induce expression of IL-1beta in human blood monocytic cells. Herein, we explore the intracellular signals and transcriptional mechanisms responsible for IL-1beta induction by FN using human promonocytic U937 cells transfected with the human IL-1beta promoter connected to a reporter gene. Exposure of transfected U937s to FN resulted in increased expression of the full-length IL-1beta promoter. This effect, mediated via the alpha5beta1 integrin, was associated with activation of mitogen-activated protein kinases (MAPKs) and was abolished by pre-treatment of cells with Calphostin C, a specific inhibitor of protein kinase C (PKC) activation. Deletion analysis and co-transfection studies using consensus activator protein 1 (AP-1) oligonucleotides suggested that an AP-1 site present in the 5' end of the IL-1beta promoter was involved in the FN-induced response. Finally, electrophoretic mobility shift assays showed that FN induced binding of AP-1, but not NF-kappaB. Together, these experiments demonstrate that FN binding to the alpha5beta1 integrin activates MAPK-dependent signal pathways, and results in the transcription of the IL-1beta promoter in U937 cells by activating PKC and inducing AP-1.
Nephrogenic Diabetes Insipidus – The Novelly Potential Therapeutic Drugs

Water reabsorption in the kidney represents a critical physiological event in the maintenance of body water homeostasis. This highly regulated process relies largely on the antidiuretic hormone, vasopressin (VP), and on the VP-sensitive aquaporin-2 (AQP2) water channel that is expressed in the principal cells of kidney collecting duct. Under normal condition, AQP2 resides in the intracellular vesicles of the principal cells. Apical plasma membrane facing the primary urine of these cells therefore contains only low amounts of water channels and is relatively water impermeable. When there is increased plasma osmolality or hypovolemia, VP released from the neurohypophysis binds to its cognate VP type 2 receptor (V2R) that is expressed on the basolateral membrane of the collecting duct principal cells. This elevates intracellular cAMP concentration and promotes protein kinase A (PKA) activity that lead to phosphorylation of AQP2 at Ser256 (Christensen et al., 2000), as well as phosphorylation of Rho at Ser188 (Tamma et al., 2001; Tamma et al., 2003). AQP2 phosphorylation allows their redistribution from intracellular location to apical plasma membrane, whereas Rho phosphorylation results in a subsequent attenuation of Rho activity that favors the depolymerization of F-actin (Tamma et al., 2001; Tamma et al., 2003). This latter action allows removal of the cytoskeleton barrier that blocks the passage of AQP2 to the plasma membrane. Therefore, with the presence of AQP2 on the apical membrane of principal cells, a strong increase of water permeability of this membrane compartment is resulted. This allows acceleration of water reabsorption from primary urine, thus compensating for body water loss during hypovolemic or hypernatremic state. Defects in the function of V2R and/or in AQP2 cell surface expression (known as nephrogenic diabetes insipidus or NDI) may perpetuate alteration of the biological boundaries that maintain plasma osmolality within a well defined, but very narrow physiological range. Patients having which are unable to concentrate their urine despite normal or elevated plasma concentrations of VP, thereby at the risk of hypernatremic dehydration and having manifestations including polyuria, polydipsia, hyposthenuria, recurrent episodes of dehydration, fever, and even growth failure. Despite the molecular defects underlying this disorder has now been revealed and has enabled a successful diagnosis, no cure is currently exists for NDI. Instead, this condition is managed by restriction in sodium intake combined with the administration of hydrochlorothiazide diuretics to reduce urine output, which might nonetheless lead to hypovolemia and
The Anti-Inflammatory Effect and Structure of EPCP1-2 from Crypthecodinium cohnii via Modulation of TLR4-NF-κB Pathways in LPS-Induced RAW 264.7 Cells

Exopolysaccharide from Crypthecodinium cohnii (EPCP1-2) is a marine exopolysaccharide that evidences a variety of biological activities. We isolated a neutral polysaccharide from the fermentation liquid of Crypthecodinium cohnii (CP). In this study, a polysaccharide that is derived from Crypthecodinium cohnii were analyzed and its anti-inflammatory effect was evaluated on protein expression of toll-like receptor 4 and nuclear factor κB pathways in macrophages. The structural characteristics of EPCP1-2 were characterized by GC (gas chromatography) and GC-MS (gas Chromatography-Mass Spectrometer) analyses. The molecular weight was about 82.5 kDa. The main chain of EPCP1-2 consisted of (1→6)-linked mannopyranosyl, (1→6)-linked glucopyranosyl, branched-chain consisted of (1→3,6)-linked galactopyranosyl and terminal consisted of t-l-Rhapyranosyl. The in vitro anti-inflammatory activity was representated through assay of proliferation rate, pro-inflammatory factor (NO) and expressions of proteins on RAW 264.7, the macrophage cell line. The results revealed that EPCP1-2 exhibited significant anti-inflammatory activity by regulating the expression of toll-like receptor 4, mitogen-activated protein kinases, and Nuclear Factor-κB protein.
Thomas Jeffery's Map of "The County of Westmoreland" (1770): an evaluation of its contribution to understanding late eighteenth century landscape

Thomas Jeffery’s map of Westmorland was one of the new county maps published in the late eighteenth century. Apart from the pursuit of profit, Jefferys’ motives in producing his map were unclear, though its contents provide clues as to what he was attempting to portray in the Westmorland landscape of the late eighteenth century. His depiction of the landscape (broadly conceived) was different in crucial respects from that provided by earlier and later cartographers. An attempt is made to evaluate his map in relation to its possible purpose.
Cell load based user association for TETRA trunk systems

Increasing traffic in communication systems need efficient new cell selection algorithms to control the distribution of users. For better and seamless transmission, load balancing become critical factors for cell selection algorithms. Un-desired consequents in these situations may cause disasters specifically for the emergency cases in public safety services. In this paper, a cell selection algorithm is proposed for Terrestrial Trunked Radio (TETRA) based Professional Mobile Radio (PMR) systems. The proposed algorithm is designed to provide a fairer distribution of users among cells while keeping the number of received power measurement less. The performances of the proposed algorithm are obtained in urban and rural environment.
Zygotic Expression of the Double-Stranded RNA Binding Motif Protein Drb2p Is Required for DNA Elimination in the Ciliate Tetrahymena thermophila

ABSTRACT Double-stranded RNA binding motif (DSRM)-containing proteins play many roles in the regulation of gene transcription and translation, including some with tandem DSRMs that act in small RNA biogenesis. We report the characterization of the genes for double-stranded RNA binding proteins 1 and 2 (DRB1 and DRB2), two genes encoding nuclear proteins with tandem DSRMs in the ciliate Tetrahymena thermophila. Both proteins are expressed throughout growth and development but exhibit distinct peaks of expression, suggesting different biological roles. In support of this, we show that expression of DRB2 is essential for vegetative growth while DRB1 expression is not. During conjugation, Drb1p and Drb2p localize to distinct nuclear foci. Cells lacking all DRB1 copies are able to produce viable progeny, although at a reduced rate relative to wild-type cells. In contrast, cells lacking germ line DRB2 copies, which thus cannot express Drb2p zygotically, fail to produce progeny, arresting late into conjugation. This arrest phenotype is accompanied by a failure to organize the essential DNA rearrangement protein Pdd1p into DNA elimination bodies and execute DNA elimination and chromosome breakage. These results implicate zygotically expressed Drb2p in the maturation of these nuclear structures, which are necessary for reorganization of the somatic genome.
Prenatal detection of cystic fibrosis by ultrasonography: a retrospective study of more than 346 000 pregnancies

Cystic fibrosis (CF) is the commonest severe autosomal recessive disease that affects children in white populations, with an incidence varying from 1/2500 to 1/5000 (carrier rate 1/25 to 1/35). 1 The disease, which is characterised by chronic pulmonary obstruction and infections, and by digestive disorders such as pancreatic insufficiency, is caused by mutations in a gene which encodes a protein called CFTR (cystic fibrosis transmembrane conductance regulator). The cloning of the CFTR gene in 19892–4 and the identification of more than 1000 mutations,5 with geographical and ethnic variations, have enabled prenatal testing for CF by direct detection of mutations. Initially, prenatal testing was only offered to families in which there was a previous history of CF. More recently, the medical assessment of pregnancy performed in some countries has allowed, through systematic ultrasound examinations, the prenatal diagnosis of bowel echogenicity, an abnormality suggestive of CF. The fetus can therefore become the proband in this disease. Fetal echogenic bowel, defined as bowel with sonographic density greater than that of the surrounding bone, is diagnosed in 0.2-1.8% of fetuses during routine ultrasound examination in the second trimester of pregnancy.6–10 This intestinal echogenicity was initially described as a normal variant, which usually disappeared at 20 weeks of gestation.11,12 More recently, it has also been associated with fetal abnormalities, such as chromosomal abnormalities,6,8,10,13–17 congenital infections,18–20 intestinal obstruction,20–22 and CF. In this latter case, it is probably the result of the malfunctioning of the CFTR protein leading to the dehydration of mucus secretions, which become viscous, obstruct the bowel lumen, and cause meconium ileus.23 The risk for CF in fetuses with echogenic bowel has been extensively studied6,9,10,13,16,20,21,24–30 and is shown …
Hypoxia‐induced catecholamine secretion in isolated newborn rat adrenal chromaffin cells is mimicked by inhibition of mitochondrial respiration

1 In newborn mammals, systemic hypoxia provokes catecholamine secretion from the adrenal medulla. In contrast to adults, this release is independent of sympathetic innervation. We have studied the cellular processes involved in hypoxia‐induced catecholamine secretion, employing fluorimetric techniques to measure changes in [Ca2+]i, NADH and mitochondrial potential, and voltammetric techniques to record changes in PO2 and catecholamine secretion. 2 In adrenal chromaffin cells freshly dissociated from newborn rats, severe hypoxia increased [Ca2+]i and secretion of catecholamines, indicating that the response of the newborn adrenal medulla to hypoxia is an intrinsic property of these cells. Discrete quantal secretory events were identifiable, suggesting an exocytotic mechanism of secretion. 3 Hypoxia‐induced secretion was only seen when PO2fell below 5 mmHg, similar to the threshold arterial PO2 reported to stimulate release in vivo. Such oxygen tensions also inhibited mitochondrial metabolism, shown by an increase in NADH autofluorescence. We therefore explored the involvement of mitochondria in oxygen sensing. Inhibition of mitochondrial respiration either by CN− at complex IV or by rotenone at complex I mimicked severe hypoxia, reversibly increasing both [Ca2+]i and catecholamine secretion. The CN−‐induced depolarization of the mitochondrial inner membrane potential preceded the increase in [Ca2]i by ∼6 s. 4 The effects of severe hypoxia and CN− on [Ca2+]i and catecholamine secretion were not additive, suggesting a common mechanism. 5 Chemical anoxia failed to increase [Ca2+]i in a significant proportion of cells dissociated from 2‐ to 4‐week‐old rats. Thus, the sensitivity to hypoxia is specific to adrenal chromaffin cells dissociated from newborn rats. 6 These data indicate that hypoxia‐induced catecholamine secretion in the newborn adrenal medulla is mediated by reversible inhibition of mitochondrial respiration, leading to an increase in [Ca2+]i and catecholamine secretion.
A 1.5–7.5GHz low power low noise amplifier (LNA) design using subthreshold technique for Wireless Sensor Network (WSN) application

A novel wide band low power low noise amplifier using subthreshold technique is presented in this paper. This LNA built with Common-Gate (CG) input stage for wide band input matching and a Common Source (CS) - Common Gate (CG) cascode stage for gain boosting. Power reduction is achieved by driving the front end CG transistor in sub-threshold region and input matching is done by LC circuit instead of traditional CG method (Rs=1/gm). The circuit is simulated using Spectra-RF simulator in 0. 18μm CMOS technology, and achieved 13.5-14.5 dB (7.5 to 8.5 dB + 6dB loss in buffer) gain over entire band of 1.5-7.5GHz with a 5-10.5dB NF while consuming 4.9mW of power from 1.8V supply.
KIR2DL4 Is an IL-2-Regulated NK Cell Receptor That Exhibits Limited Expression in Humans but Triggers Strong IFN-γ Production1

Killer cell Ig-like receptor (KIR)2DL4 (2DL4, CD158d) was previously described as the only KIR expressed by every human NK cell. It is also structurally atypical among KIRs because it possesses a basic transmembrane residue, which is characteristic of many activating receptors, but also contains a cytoplasmic immunoreceptor tyrosine-based inhibitory motif (ITIM). We expressed epitope-tagged 2DL4 in an NK-like cell line to study receptor function. Three distinct 2DL4 cDNA clones were analyzed: one encoding the “conventional” 2DL4 with the cytoplasmic ITIM (2DL4.1) and two encoding different cytoplasmic truncated forms lacking the ITIM (2DL4.2 and 2DL4∗). Surprisingly, one truncated receptor (2DL4.2), which is the product of a prevalent human 2DL4 allele, was not expressed on the cell surface, indicating that some individuals may lack functional 2DL4 protein expression. Conversely, both 2DL4.1 and 2DL4∗ were expressed on the cell surface and up-regulated by IL-2. Analysis of primary NK cells with anti-2DL4 mAb confirmed the lack of surface expression in a donor with the 2DL4.2 genotype. Donors with the 2DL4.1 genotype occasionally expressed receptor only on CD56high NK cells, although their expression was up-regulated by IL-2. Interestingly, Ab engagement of epitope-tagged 2DL4 triggered rapid and robust IFN-γ production, but weak redirected cytotoxicity in an NK-like cell line, which was the opposite pattern to that observed upon engagement of another NK cell activating receptor, NKp44. Importantly, both 2DL4.1 and 2DL4∗ exhibited similar activation potential, indicating that the ITIM does not influence 2DL4.1 activating function. The unique activation properties of 2DL4 suggest linkage to a distinct signaling pathway.
Efficient DNA Transfection Mediated by the C-Terminal Domain of Human Immunodeficiency Virus Type 1 Viral Protein R

ABSTRACT Viral protein R (Vpr) of human immunodeficiency virus type 1 is produced late in the virus life cycle and is assembled into the virion through binding to the Gag protein. It is known to play a significant role early in the viral life cycle by facilitating the nuclear import of the preintegration complex in nondividing cells. Vpr is also able to interact with nucleic acids, and we show here that it induces condensation of plasmid DNA. We have explored the possibility of using these properties in DNA transfection experiments. We report that the C-terminal half of the protein (Vpr52–96) mediates DNA transfection in a variety of human and nonhuman cell lines with efficiencies comparable to those of the best-known transfection agents. Compared with polylysine, a standard polycationic transfection reagent, Vpr52–96 was 10- to 1,000-fold more active. Vpr52–96-DNA complexes were able to reach the cell nucleus through a pH-independent mechanism. These observations possibly identify an alternate pathway for DNA transfection.
Haemodynamics during a complete exercise induced atrioventricular block

The case is reported of an athlete who, during an exercise test, had a complete atrioventricular block without symptoms of cardiac output failure. Heart rate, stroke index, cardiac index, and myocardial contractility were monitored during the episode by an impedance cardiograph. The most important findings of this report are the continuous increase in stroke index, which compensated for the lack of heart rate response, and the normal cardiac index values achieved during the exercise. This stroke index response was mainly due to an increase in myocardial contractility.
A global genomic view of MIF knockdown-mediated cell cycle arrest

Macrophage immigration inhibitory factor (MIF) is a ubiquitously expressed proinflammatory mediator that has also been implicated in cell growth, cell cycle and carcinogenesis. In this study, we demonstrate siRNA-mediated knockdown of MIF results in G0/G1 cell cycle arrest in HEK293 cells. To elucidate the molecular mechanism of cell cycle perturbation following MIF knockdown, we employed microarray to investigate the genome-wide expression profile in MIF-deficient cells and normal cells. Quantitative real-time PCR were used to confirm the differential expression patterns of ~50 transcripts involved in cell cycle and signaling identified by microarray. The dynamic model of MIF-dependent signaling pathways linked to cell cycle machinery were constructed through analyzing gene expression data in the context of known biological pathways. The results demonstrate that knockdown of MIF could inhibit G1/S transition through inhibition of MAPK, PI3K/Akt, NF-κB, c-Myc-dependent pathway and activation of TGF-β, p53-dependent pathway. Meanwhile, inhibition of E2F-, NFκB, c-Myc, and Ap-1-mediated transcription and stimulation of p53 and FoxO4 transcriptional activity will lead to differential expression of cell cycle regulators and subsequent cell cycle arrest in G0/G1 phase in MIF-knockdown cells. This study provides novel insights into the pleiotropic activities of endogenous MIF, especially its essential and crucial role in cell proliferation and the cell cycle.
A formal verification environment for use in the certification of safety-related C-programs

In this thesis the design and the development of an environment for the formal verification of functional properties of safety-related software written in the programming language C is described. The main focus lies on the partly automated and partly user-guided verification of non-trivial mathematical computations that play an important role in modern sensor technology, among others. The demonstration of the correctness of these computations is an absolute prerequisite for their approval by a certification authority. The relevant legal and normative setting is analysed at the beginning of this work, which applies to safety-related systems that make use of programmable electronic devices and software in particular. There are three major achievements contained in this work. Firstly, a formal connection is established between the expressive language of higher-order logic, as it is formalised in the theorem prover Isabelle, and a specification language which stays close to the syntax and semantics of the programming language and which lies in the tradition of the design by contract methodology. This connection allows to specify functional properties of programs in a code-centric and at the same time appropriately abstract fashion, so that the clean mathematical character of higher-level specifications is retained. Secondly, a memory model for the programming language C is formalised within the theorem prover Isabelle which is sufficiently detailed to model low-level memory operations while still keeping the entailed verification overhead in tolerable bounds. Finally, a denotational semantics for a subset of C is formally defined and a Hoare style proof calculus is derived from it such that the correctness of programs with respect to their specifications can be shown in one integrated framework. The applicability of the approach is demonstrated by describing its use in a real project. Concretely, a substantial number of the verification measures stipulated by an international safety standard for safety-related software is covered by employing the verification environment described here. The compliance of both the safety-related software developed in the project as well as the verification environment itself have been officially asserted by a responsible certification authority.
Content-based gamut mapping algorithm for multiple engine printing

Gamut mapping is a critical process in the output color management of a printer. In systems consisting of two or more marking engines, these engines could in general have different output color gamuts. In special cases these gamuts can be drastically different. When applying gamut mapping to a multi-engine printing system, which gamut to use is not obvious. In the default case, i.e., if the multi-engine system is treated as a single engine with a single gamut, poor image quality could result. In this paper, we propose gamut mapping strategies for multiple engine printing, which depend on the relative importance of "color rendition" and "page-to-page color consistency" within a given document. In particular, we propose a content-based gamut mapping, wherein the trade-offs between color rendition and page-to-page color consistency can be automatically and dynamically made by segmenting the document and applying gamut mapping according to the needs of the segmented components.
GPU processing of theta‐joins

The GPGPU paradigm has recently been employed to accelerate the processing of big amounts of data through the utilization of the massive parallelism offered by modern GPUs. To date, several techniques have been proposed for the implementation of simple select, aggregate, and equality join operations on GPUs. In this paper, we study the efficient implementation of theta‐join queries between two relations using the CUDA framework. Theta‐joins are notoriously slow and thus can benefit from massively parallel execution. However, their GPU‐based implementation significantly differs from hash‐ and sort‐based equality joins and needs to be carefully crafted. The implementation is driven by two main objectives. The first relates to the attainment of high efficiency in the parallelization through data reuse, which relates to the minimization of accesses to the slow global memory. The second is about the most efficient exploitation of the available memory given that, in general, it cannot hold the entire input and result. We propose a methodology for processing theta‐joins on a GPU, which exploits the heterogeneous nature of GPGPU, while addressing memory limitations. Furthermore, we provide a series of implementation optimizations, which yield performance improvements of an order of magnitude.