Miracle-dz/UniFAR-FTUs huggingface dataset:
Expression of a soluble triggering receptor expressed on myeloid cells‐1 (sTREM‐1) correlates with clinical disease activity in intestinal Behcet's disease

Background: No serological marker currently exists to assess disease activity in patients with intestinal Behcet's disease (BD). We conducted this study to determine if the expression level of serum soluble triggering receptor expressed on myeloid cells‐1 (sTREM‐1) can be used as a biological marker to assess disease activity in intestinal BD. Methods: A total of 88 patients with intestinal BD were enrolled prospectively. We assessed their clinical disease activities using the disease activity index for intestinal BD (DAIBD). At the time that the DAIBD was assessed, serum erythrocyte sedimentation rate (ESR) as well as levels of TREM‐1, C‐reactive protein (CRP), and tumor necrosis factor‐&agr; (TNF‐&agr;) were measured. Results: The mean ESR and mean levels of sTREM‐1, CRP, and TNF‐&agr; in patients with intestinal BD were significantly higher than those in healthy controls. Levels of sTREM‐1 were the most highly correlated with disease activity (r = 0.762 for the DAIBD score), followed by CRP levels (r = 0.383 for the DAIBD score) and ESR (r = 0.236 for the DAIBD score). However, serum levels of TNF‐&agr; level were not correlated with disease activity (r = −0.017 for the DAIBD score). Conclusions: Serum sTREM‐1 levels were more highly correlated with disease activity than were CRP levels or ESR in patients with intestinal BD, suggesting that serum sTREM‐1 level could be a potential marker for the assessment of disease activity of intestinal BD. (Inflamm Bowel Dis 2011;)
LEDGINs, non-catalytic site inhibitors of HIV-1 integrase: a patent review (2006 – 2014)

Introduction: Integration of the viral genome into the host cell chromatin is a central step in the replication cycle of the HIV. Blocking the viral integrase (IN) enzyme therefore provides an attractive therapeutic strategy, as evidenced by the recent clinical approval of three IN strand transfer inhibitors. Viral resistance and cross-resistance among these inhibitors, however, warrant the search for compounds targeting HIV integration through alternative mechanisms of action. Areas covered: The most potent class of allosteric IN inhibitors was independently identified at the University of Leuven, Belgium, and at Boehringer Ingelheim, Canada. These compounds, coined LEDGINs (after the lens epithelium-derived growth factor/p75 cofactor binding pocket on IN) or non-catalytic site IN inhibitors (NCINIs) by the respective groups, have shown remarkable antiviral activity. This review provides a brief introduction to the compound class and discusses the recent patent literature (2006 to the present). Expert opinion: LEDGINs are still early in development. Trials with clinical candidate BI-224436 were put on hold despite promising results. Literature, however, reveals that almost all major pharmaceutical companies active in the treatment of HIV/AIDS have taken a significant interest in this class. As a result, several of these inhibitors may soon enter clinical trials.
The cellular proto-oncogene product Myb acts as transcriptional activator of the long terminal repeat of human T-lymphotropic virus type I

The proto-oncogene c-myb encodes a nuclear transcription factor that binds to DNA in a sequence-specific manner and activates transcription of several viral and cellular genes. Expression of the c-myb gene is induced in mitogen- and/or antigen-stimulated T lymphocytes, which are also the preferential target cells of human T-lymphotropic virus type I (HTLV-I) in vivo and in vitro. We report here that Myb binds to the HTLV-I long terminal repeat (LTR) in four different regions in a sequence-specific manner. Electrophoretic mobility shift assay using labeled LTR fragments as well as labeled double-stranded oligonucleotides show that there are two high-affinity and two low-affinity Myb-binding sites present in the HTLV-I LTR. DNase I footprinting analysis and oligonucleotide competition experiments indicate that this binding is sequence specific. Cotransfection experiments in HeLa cells, using a Myb expression vector and chloramphenicol acetyltransferase reporter gene linked to the HTLV-I LTR, show that Myb activates HTLV-I LTR-mediated transcription by a factor of four-to sixfold. Thus, in HTLV-I-infected T cells, Myb protein binding to the HTLV-I LTR may constitute one of the signal that regulate HTLV-I transcription in vivo.
Molecular cloning of a gene involved in lipooligosaccharide biosynthesis and virulence expression by Haemophilus influenzae type B

A wild‐type Haemophilus influenzae type b (Hib) genomic DNA library was constructed in the plasmid shuttle vector pGJB103. A virulence‐deficient lipooligosaccharide (LOS) mutant of Hib was used as a recipient for genetic transformation to screen this Hib genomic DNA library for genes involved in LOS expression. A recombinant plasmid containing a 7.8 kb Pstl fragment of Hib DNA was shown to transform this LOS mutant to reactivity with a monoclonal antibody (mAb) specific for a wild‐type LOS epitope. Transformation of two different virulence‐deficient LOS mutants with a 4.4kb BglII fragment of this recombinant plasmid yielded transformants which expressed LOS that bound the wild‐type LOS‐specific mAb and yielded profiles in sodium dodecyl sulphate/polyacrylamide gradient gel electrophoresis different from those of the original LOS mutants. These transformants with structurally altered LOS molecules also exhibited increased virulence in an animal model for invasive Hib disease. The virulence‐transforming ability was further localized to a 1.8kb BglII‐AlwNI fragment of the Hib DNA insert. Nucleotide sequence analysis indicated the presence of a single large open reading frame within this fragment. This open reading frame contained 19 consecutive repeats of the tetramer CAAT near the 5’end. Linker insertion mutagenesis was used to demonstrate directly the involvement of this open reading frame in both LOS biosynthesis and virulence expression by Hib.
Changes in the epidemiology of sudden infant death syndrome in Sweden 1973–1996

BACKGROUND From the early 1970s to the early 1990s, there was a significant rise in the incidence of sudden infant death syndrome (SIDS) in Scandinavia. Following the risk reducing campaign, the incidence has fallen to about the same level as in 1973. AIMS To identify the changes that have occurred in the epidemiology of SIDS. METHODS We compared the Swedish part of the Nordic Epidemiological SIDS Study (NESS), covering the years 1992–1995, with two earlier, descriptive studies during this period. To assess the changing effects of risk factors, we analysed data from the Medical Birth Registry of Sweden, covering the years 1973–1996. RESULTS There was a predominance of deaths during weekends in the 1970s and 1990s. The seasonal variation was most notable in the 1980s. The proportion of young mothers decreased from 14% to 5%. Cohabitation (living with the biological father) was as frequent in the 1990s as in the 1970s. The prevalence of high parity, admissions to neonatal wards, low birth weight, prematurity, and multiple pregnancies were all increased in the 1990s compared to the 1970s. No significant change in the prevalence of previous apparent life threatening events was found. Deaths occurring in cars diminished from 10% to below 2%. In the data from the Medical Birth Registry of Sweden, there were significantly increased odds ratios after the risk reducing campaign of the risk factors smoking during early pregnancy and preterm birth. We could find no increased effects of maternal age, parity, or being small for gestational age over time. The rate of deaths at weekends remained increased; the median age at death fell from 90 to 60 days. Seasonal variation was less notable in the periods of low incidence. Key messages SIDS incidence in Sweden declined from 1.1 per 1000 live births in 1991 to 0.3 in 1999 The predominance of deaths at weekends remained Deaths in cars declined Age at death decreased from 90 to 60 days Seasonality was less notable in periods of low incidence Odds ratios increased for smoking and prematurity
Stability of randomly amplified polymorphic DNA fingerprinting in genotyping clinical isolates of Helicobacter pylori.

AIM H pylori genomes are highly diversified. This project was designed to genotype H pylori isolates by the polymerase chain reaction (PCR)-based randomly amplified polymorphic DNA (RAPD) fingerprinting technique and to verify its stability by Southern blotting and DNA sequencing. METHODS Clinical isolates of H pylori were cultured from gastric antra and cardia of 73 individuals, and genomic DNA was prepared for each isolate. RAPD was carried out under optimized conditions. 23S rDNA was regarded as an internal control, and a 361 bp rDNA fragment (RDF) was used as a probe to screen the RAPD products by Southern blotting. Ten RDFs from different clinical isolates and the flanking regions (both upstream and downstream) of four RDFs were amplified and sequenced. RESULTS H pylori isolates from different individuals had different RAPD profiles, but the profiles for isolates cultured from different gastric sites of a given individual were identical in all but one case. Isolates from 27 individuals were RDF positive by Southern blotting. Sequences of the RDFs and their flanking regions were almost the same between the RDF positive and negative isolates as determined by Southern blotting. There was no binding site for random PCR primer inside the sequences. CONCLUSION RAPD is very useful in genotyping H pylori grossly on a large scale. However, it seems unstable in amplification of low yield fragments, especially those that do not appear as visible bands on the agarose gel stained with EB, since the primer is partially matched to the template.
Molecular diversity of fungal and bacterial communities in the marine sponge Dragmacidon reticulatum

The present work aimed to investigate the diversity of bacteria and filamentous fungi of southern Atlantic Ocean marine sponge Dragmacidon reticulatum using cultivation‐independent approaches. Fungal ITS rDNA and 18S gene analyses (DGGE and direct sequencing approaches) showed the presence of representatives of three order (Polyporales, Malasseziales, and Agaricales) from the phylum Basidiomycota and seven orders belonging to the phylum Ascomycota (Arthoniales, Capnodiales, Dothideales, Eurotiales, Hypocreales, Pleosporales, and Saccharomycetales). On the other hand, bacterial 16S rDNA gene analyses by direct sequencing approach revealed the presence of representatives of seven bacterial phyla (Cyanobacteria, Proteobacteria, Actinobacteria, Bacteroidetes, Lentisphaerae, Chloroflexi, and Planctomycetes). Results from statistical analyses (rarefaction curves) suggested that the sampled clones covered the fungal diversity in the sponge samples studied, while for the bacterial community additional sampling would be necessary for saturation. This is the first report related to the molecular analyses of fungal and bacterial communities by cultivation‐independent approaches in the marine sponges D. reticulatum. Additionally, the present work broadening the knowledge of microbial diversity associated to marine sponges and reports innovative data on the presence of some fungal genera in marine samples.
Resolving the Motional Modes That Code for RNA Adaptation

Using a domain elongation strategy, we decoupled internal motions in RNA from overall rotational diffusion. This allowed us to site-specifically resolve a manifold of motional modes in two regulatory RNAs from HIV-1 with the use of nuclear magnetic resonance spin relaxation methods. Base and sugar librations vary on a picosecond time scale and occur within helical domains that move collectively at diffusion-limited nanosecond time scales. Pivot points are short, functionally important, and highly mobile internal loops. These spontaneous changes in RNA conformation correlate quantitatively with those that follow adaptive recognition of diverse targets. Thus, ligands may stabilize existing RNA conformations rather than inducing new ones.
Lichtenstein inguinal hernia repair in a primary healthcare setting

Given the generally accepted poor outcome of inguinal hernia repair when using nylon darn, and the recent interest in low‐tension mesh repair, an attempt was made to demonstrate the feasibility, outcome and patient perception of providing Lichtenstein inguinal hernia repair, using local anaesthesia, wholly within the primary healthcare sector.
Cell/surface interactions on laser-micro-textured titanium-coated silicon surfaces

This paper presents the results of recent efforts to improve the biocompatibility and integration of implantable bioMEMS devices. Laser micro-grooves and micro-grids were irradiated onto silicon surfaces using ultraviolet lasers. The micro-textured surfaces were then coated with nano-scale layers of titanium to promote improved biocompatibility. The micro-groove geometries have been shown to promote contact guidance, which leads to reduced scar tissue formation. In contrast, smooth surfaces result in random cell orientations and the increased possibility of scar tissue formation. The nature of the cellular attachment and adhesion to the coated/uncoated micro-textured surfaces was elucidated by the visualization of the cells through scanning electron microscopy. Finally, the implications of the results are discussed for integration of silicon-based microelectronics and sensors into biological systems.
Comparison of Label-free Methods for Quantifying Human Proteins by Shotgun Proteomics*S

Measurements of mass spectral peak intensities and spectral counts are promising methods for quantifying protein abundance changes in shotgun proteomic analyses. We describe Serac, software developed to evaluate the ability of each method to quantify relative changes in protein abundance. Dynamic range and linearity using a three-dimensional ion trap were tested using standard proteins spiked into a complex sample. Linearity and good agreement between observed versus expected protein ratios were obtained after normalization and background subtraction of peak area intensity measurements and correction of spectral counts to eliminate discontinuity in ratio estimates. Peak intensity values useful for protein quantitation ranged from 107 to 1011 counts with no obvious saturation effect, and proteins in replicate samples showed variations of less than 2-fold within the 95% range (±2ς) when ≥3 peptides/protein were shared between samples. Protein ratios were determined with high confidence from spectral counts when maximum spectral counts were ≥4 spectra/protein, and replicates showed equivalent measurements well within 95% confidence limits. In further tests, complex samples were separated by gel exclusion chromatography, quantifying changes in protein abundance between different fractions. Linear behavior of peak area intensity measurements was obtained for peptides from proteins in different fractions. Protein ratios determined by spectral counting agreed well with those determined from peak area intensity measurements, and both agreed with independent measurements based on gel staining intensities. Overall spectral counting proved to be a more sensitive method for detecting proteins that undergo changes in abundance, whereas peak area intensity measurements yielded more accurate estimates of protein ratios. Finally these methods were used to analyze differential changes in protein expression in human erythroleukemia K562 cells stimulated under conditions that promote cell differentiation by mitogen-activated protein kinase pathway activation. Protein changes identified with p < 0.1 showed good correlations with parallel measurements of changes in mRNA expression.
Numerical microdosimetry of complex shaped cell models in electroporation

In this paper, the FEM (finite element method) for the quasi static condition has been applied to evaluate the EM field interaction with the cells in different shapes, such as ellipsoid. The influences of the cells shape and its orientation to the applied electric field have been assessed. The results obtained have cast light on a number of observations in the process of electroporation.
The Embryotrophic Activity of Oviductal Cell-derived Complement C3b and iC3b, a Novel Function of Complement Protein in Reproduction*

The oviduct-derived embryotrophic factor, ETF-3, enhances the development of trophectoderm and the hatching process of treated embryos. Monoclonal anti-ETF-3 antibody that abolishes the embryotrophic activity of ETF-3 recognized a 115-kDa protein from the conditioned medium of immortalized human oviductal cells. Mass spectrometry analysis showed that the protein was complement C3. Western blot analysis using an antibody against C3 confirmed the cross-reactivities between anti-C3 antibody with ETF-3 and anti-ETF-3 antibody with C3 and its derivatives, C3b and iC3b. Both derivatives, but not C3, were embryotrophic. iC3b was most efficient in enhancing the development of blastocysts with larger size and higher hatching rate, consistent with the previous reported embryotrophic activity of ETF-3. Embryos treated with iC3b contained iC3b immunoreactivity. The oviductal epithelium produced C3 as evidenced by the presence of C3 immunoreactivity and mRNA in the human oviduct and cultured oviductal cells. Cyclical changes in the expression of C3 immunoreactivity and mRNA were also found in the mouse oviduct with the highest expression at the estrus stage. Molecules involving in the conversion of C3b to iC3b and binding of iC3b were present in the human oviduct (factor I) and mouse preimplantation embryo (Crry and CR3), respectively. In conclusion, the present data showed that the oviduct produced C3/C3b, which was converted to iC3b to stimulate embryo development.
Social control in therapeutic communities for the treatment of drug addicts.

There is a saying among the residents of the Synanon-type therapeutic community Phoenix House that if ten people in an encounter group tell you long enough and loud enough that you are a horse, eventually you find yourself putting on a saddle. This saying is told to illustrate the power of group consensus and social control in this type of therapeutic community.
Fast and slow components of cerebral blood flow response to step decreases in end-tidal PCO2 in humans.

This study examined the dynamics of the middle cerebral artery (MCA) blood flow response to hypocapnia in humans (n = 6) by using transcranial Doppler ultrasound. In a control protocol, end-tidal PCO2 (PETCO2) was held near eucapnia (1.5 Torr above resting) for 40 min. In a hypocapnic protocol, PETCO2 was held near eucapnia for 10 min, then at 15 Torr below eucapnia for 20 min, and then near eucapnia for 10 min. During both protocols, subjects hyperventilated throughout and PETCO2 and end-tidal PO2 were controlled by using the dynamic end-tidal forcing technique. Beat-by-beat values were calculated for the intensity-weighted mean velocity (VIWM), signal power (P), and their instantaneous product (P.VIWM). A simple model consisting of a delay, gain terms, time constants (tauf,on, tauf, off) and baseline levels of flow for the on- and off-transients, and a gain term (gs) and time constant (taus) for a second slower component was fitted to the hypocapnic protocol. The cerebral blood flow response to hypocapnia was characterized by a significant (P < 0.001) slow progressive adaptation in P.VIWM, with gs = 1.26 %/Torr and taus = 427 s, that persisted throughout the hypocapnic period. Finally, the responses at the onset and relief of hypocapnia were asymmetric (P < 0.001), with tauf,on (6.8 s) faster than tauf,off (14.3 s).
Glibenclamide-induced blockade of ischemic preconditioning is time dependent in intact rat heart.

The ATP-sensitive potassium (KATP) channel has been demonstrated to be a potential mediator of ischemic preconditioning (PC) in most species, with the exception of the rat. This conclusion is based on the failure of the KATP channel antagonist glibenclamide (Glib) to block PC in this species. However, previous studies did not take into consideration the kinetic properties of Glib binding to its receptor in the rat myocardium. Therefore, the purpose of the present study was to test the hypothesis that ischemic PC is mediated by the myocardial KATP channel in the rat and that blockade of PC by Glib is a time-dependent phenomenon. Barbiturate-anesthetized, open-chest male Wistar rats were subjected to 30 min of occlusion and 2 h of reperfusion. Ischemic PC was elicited by three 5-min occlusion periods interspersed with 5 min of reperfusion. Infarct size (IS) as a percentage of the area at risk (AAR; IS/AAR) was determined with triphenyltetrazolium staining. PC and the KATP channel opener nicorandil (50 micrograms.kg-1.min-1 i.v.) resulted in marked reductions in IS/AAR from 53 +/- 3% to 8 +/- 1% and 17 +/- 5%, respectively (P < 0.05). Two doses of Glib (1 or 0.3 mg/kg i.v.) given 30 min before PC abolished the protective effect of PC; however, Glib (0.3 mg/kg i.v.) given 5 min before PC failed to block the effect. Glib administered 30 min before the 15-min nicorandil infusion blocked the cardioprotective effect of NC but did not block its transient hypotensive effect. These results demonstrate that the KATP channel is involved in ischemic PC in the intact rat heart and that the inhibitory effect of Glib to block PC is time dependent.
A non-intrusive, operating system independent spinlock profiler for embedded multicore systems

Locks are widely used as a synchronization method to guarantee the mutual exclusion for accesses to shared resources in multi-core embedded systems. They have been studied for years to improve performance, fairness, predictability etc. and a variety of lock implementations optimized for different scenarios have been proposed. In practice, applying an appropriate lock type to a specific scenario is usually based on the developer's hypothesis, which could mismatch the actual situation. A wrong lock type applied may result in lower performance and unfairness. Thus, a lock profiling tool is needed to increase the system transparency and guarantee the proper lock usage. In this paper, an operating-system-independent lock profiling approach is proposed as there are many different operating systems in the embedded field. This approach detects lock acquisition and lock releasing using hardware tracing based on hardware-level spinlock characteristics instead of specific libraries or APIs. The spinlocks are identified automatically; lock profiling statistics can be measured and performance-harmful lock behaviors are detected. With this information, the lock usage can be improved by the software developer. A prototype as a Java tool was implemented to conduct hardware tracing and analyze locks inside applications running on the Infineon AURIX microcontrollers.
The importance of genomic novelty in social evolution

Insect societies dominate the natural world: They mould landscapes, sculpt habitats, pollinate plants, sow seeds and control pests. The secret to their success lies in the evolution of queen (reproductive) and worker (provisioner and carer) castes (Oster & Wilson ). A major problem in evolutionary biology is explaining the evolution of insect castes, particularly the workers (Darwin ). Next‐generation sequencing technologies now make it possible to understand how genomic material is born, lost and reorganized in the evolution of alternative phenotypes. Such analyses are revealing a general role for novel (e.g. taxonomically restricted) genes in phenotypic innovations across the animal kingdom (Chen et al. 2013). In this issue of molecular ecology, Feldmeyer et al. (2014) provide overwhelming evidence for the importance of novel genes in caste evolution in an ant. Feldmeyer et al.'s study is important and exciting because it cements the role of genomic novelty, as well as conservation, firmly into the molecular jigsaw of social evolution. Evolution is eclectic in its exploitation of both old and new genomic material to generate replicated phenotypic innovations across the tree of life.