gebhart/patrepeval huggingface dataset:
NadA Diversity and Carriage in Neisseria meningitidis (2004)

NadA is a novel vaccine candidate recently identified in Neisseria meningitidis and involved in adhesion to host tissues. The nadA gene has been found in approximately 50% of the strains isolated from patients and in three of the four hypervirulent lineages of non-serogroup A strains. Here we investigated the presence of the nadA gene in 154 meningococcal strains isolated from healthy people (carrier strains). Only 25 (16.2%) of the 154 carrier isolates harbored the nadA gene. The commensal species Neisseria lactamica was also found not to have the nadA gene. Eighteen of the carrier strains belonged to the ET-5 and ET-37 hypervirulent clusters, indicating that only the 5.1% of the genuine carrier population actually harbored nadA (7 of 136 strains). Five of the seven strains harbored a novel allele of the nadA gene that was designated nadA4. The NadA4 protein was present on the bacterial surface as heat-stable high-molecular-weight oligomers. Antibodies against the recombinant NadA4 protein were bactericidal against homologous strains, whereas the activity against other NadA alleles was weak. In conclusion, the nadA gene segregates differently in the population of strains isolated from healthy individuals and in the population of strains isolated from patients. The presence of NadA can therefore be used as a tool to study the dynamics of meningococcal infections and understand why this bacterium, which is mostly a commensal, can become a severe pathogen.
A new strategy for genome assembly using short sequence reads and reduced representation libraries (2010)

We have developed a novel approach for using massively parallel short-read sequencing to generate fast and inexpensive de novo genomic assemblies comparable to those generated by capillary-based methods. The ultrashort (<100 base) sequences generated by this technology pose specific biological and computational challenges for de novo assembly of large genomes. To account for this, we devised a method for experimentally partitioning the genome using reduced representation (RR) libraries prior to assembly. We use two restriction enzymes independently to create a series of overlapping fragment libraries, each containing a tractable subset of the genome. Together, these libraries allow us to reassemble the entire genome without the need of a reference sequence. As proof of concept, we applied this approach to sequence and assembled the majority of the 125-Mb Drosophila melanogaster genome. We subsequently demonstrate the accuracy of our assembly method with meaningful comparisons against the current available D. melanogaster reference genome (dm3). The ease of assembly and accuracy for comparative genomics suggest that our approach will scale to future mammalian genome-sequencing efforts, saving both time and money without sacrificing quality.
Inhibition of complement alternative pathway in mice with Fab antibody to recombinant adipsin/factor D (1993)

Mouse adipsin is a serine protease secreted mainly by adipocytes. Similarly to factor D of human complement, it cleaves factor B. That adipsin is the equivalent of human factor D in the mouse is further suggested by their structural homology. Specific antisera against recombinant mouse adipsin (r-adipsin) were produced in rabbits. Anti-r-adipsin IgG was shown to bind to radiolabeled r-adipsin and to inhibit its hemolytic activity. In vitro, these antibodies Ab and Fab fragments thereof inhibited the adipsin/factor D hemolytic activity of mouse serum. They also blocked C3 activation induced by cobra venom factor (CVF), but did not interfere with classical pathway function. After intravenous injection of anti-r-adipsin Fab into BALB/c mice, the adipsin/factor D hemolytic activity of serum was abolished during a 4-h period. The C3 depleting effect of CVF injected intravenously was significantly delayed in BALB/c mice which had been pretreated with anti-r-adipsin Fab. These experiments demonstrate that mouse adipsin is the only form of mouse factor D and that anti-r-adipsin antibody can be used to produce a specific inhibition of the alternative pathway in vivo.
Induction of cre recombinase activity using modified androgen receptor ligand binding domains: a sensitive assay for ligand-receptor interactions (2003)

Novel systems of inducible gene expression are presented in which CRE-M, an altered form of cre recombinase (cre), is fused to and activated by ligand binding to two forms of the androgen receptor (AR) ligand binding domain (LBD). Selective activation or inactivation of gene transcription is induced upon the addition of appropriate ligand. The coupling of this cre-LBD system with our previously reported highly sensitive assay to measure cre activity in vitro using a dual fluorescent gene switch reporter provides a novel, high-throughput assay system for identifying compounds that bind to and activate various forms of the LBD of androgen receptor. This method can similarly be applied to screen compounds for their activating properties on other steroid hormone LBDs. Three different forms of the AR-LBD were fused to CRE-M, including the wild-type AR-LBD (wt), a non-ligand binding truncated form, LBD (T), and a mutated form (Thr-->Ala substitution) identified in the LNCaP prostate cancer cell line, LBD (LNCaP). We demonstrate a 10-fold induction of cre activity by the addition of androgen agonists to the CRE-M-AR-LBD(wt) fusion protein, but not in the presence of the anti-androgen, flutamide. However, cre activity can be induced by flutamide with the CRE-M-AR-LBD(LNCaP) fusion protein. Similar activation properties were obtained when these fusion proteins were expressed using adenoviral vectors. When combined with our previously reported cre-lox gene switch system, the CRE-M-AR-LBD system can be utilized in gene therapy systems in which a therapeutic product may be initially expressed, replaced by a second product, or turned-off following exposure to ligand. This provides an important, additional level of regulation to gene therapy systems.
Prologue (2003)

In 1580 King Philip II of Spain completed the 800-year-old dream of uniting the Iberian peninsula under one Christian ruler. With the addition of Portugal and its overseas empire to his domains, Philip ruled a vast expanse of territory that could only be measured in continents: the newly discovered Americas, coastal forts in Africa, outposts in Asia, and large sections of western Europe. His merchants spanned the globe, providing spices, sugar, slaves, silver, and gold to the growing European markets. Diplomats and scholars throughout Europe spoke Philip's language — Castilian — and sported Spanish fashions, implicitly recognizing the super-power of the age.KeywordsSurface DisturbancePeasant MovementConventional NarrativeHistorical EnterpriseMomentary AttentionThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
Improved siRNA delivery efficiency via solvent-induced condensation of micellar nanoparticles (2017)

Efficient delivery of short interfering RNA (siRNA) remains one of the primary challenges of RNA interference therapy. Polyethylene glycol (PEG)ylated polycationic carriers have been widely used for the condensation of DNA and RNA molecules into complex-core micelles. The PEG corona of such nanoparticles can significantly improve their colloidal stability in serum, but PEGylation of the carriers also reduces their condensation capacity, hindering the generation of micellar particles with sufficient complex stability. This presents a particularly significant challenge for packaging siRNA into complex micelles, as it has a much smaller size and more rigid chain structure than DNA plasmids. Here, we report a new method to enhance the condensation of siRNA with PEGylated linear polyethylenimine using organic solvent and to prepare smaller siRNA nanoparticles with a more extended PEG corona and consequently higher stability. As a proof of principle, we have demonstrated the improved gene knockdown efficiency resulting from the reduced siRNA micelle size in mice livers following intravenous administration.
Rationale and design of dal-VESSEL: a study to assess the safety and efficacy of dalcetrapib on endothelial function using brachial artery flow-mediated vasodilatation (2010)

Objective:Dalcetrapib increases high-density lipoprotein cholesterol (HDL-C) levels through effects on cholesteryl ester transfer protein (CETP). As part of the dalcetrapib dal-HEART clinical trial programme, the efficacy and safety of dalcetrapib is assessed in coronary heart disease (CHD) patients in the dal-VESSEL study (ClinicalTrials.gov identifier: NCT00655538), the design and methods of which are presented here.Research design and study method:Men and women with CHD or CHD risk equivalent, with HDL-C levels <50 mg/dL were recruited for a 36-week, double-blinded, placebo-controlled trial. After a pre-randomisation phase of up to 8 weeks, patients received dalcetrapib 600 mg/day or placebo in addition to their existing treatments. Brachial flow-mediated dilatation (FMD) measured by B-mode ultrasound represents endothelial function and is a validated marker for early atherosclerosis and cardiovascular disease risk.Main outcome measures:The primary efficacy outcome is change from baseline in brachial FMD after 12 weeks. The primary safety endpoint is 24-hour ambulatory blood pressure monitoring (ABPM) assessed at week 4. Secondary endpoints include brachial FMD at 36 weeks, ABPM at 12 and 36 weeks, lipid profile, CETP mass and activity, and markers of inflammation, oxidation, and cardiovascular risk. Clinical endpoints are assessed as a composite endpoint for the dal-HEART Program.Current status:In 19 European clinical centres, 476 subjects met inclusion criteria and have entered the study. In conclusion, the dal-VESSEL study is the largest multicentre trial with brachial FMD ever performed. The study assesses efficacy and safety of dalcetrapib on endothelial function, blood pressure, lipids, and clinical outcomes in CHD patients with below average HDL-C and will therefore provide vital information regarding its potential role in the preventative treatment of CHD risk.Trial registration: ClinicalTrials.gov identifier: NCT00655538.
Nucleotide sequence of a cDNA for the chickyesproto-oncogene: comparison with the viralyesgene (1988)

We present the nucleotide sequence of a 1.8 kb cDNA clone (p6A) isolated from
Hybrid Sensor-Camera Monitoring for Damage Detection: Case Study of a Real Bridge (2016)

This article presents the real-world implementation of a novel monitoring system in which video images and conventional sensor network data are simultaneously analyzed to detect possible damage on a movable bridge. The monitoring system was designed to detect such problems at the onset of damage. A video stream of traffic is processed to detect and classify vehicles to determine the vehicle load and location, while strain measurements are simultaneously collected at various critical locations on the bridge for both normal and damage conditions. A series of unit influence lines can then be extracted for all of the scenarios using the image and sensor data. Because large data sets result from continuous monitoring, the system also includes a statistical outlier-detection algorithm. The proposed methodology was successfully used to detect and locate common damage scenarios on a real-world bascule bridge.
Fagus sylvaticaglucuronoxylan sulfate−chemical profile and pharmacological view (2015)

Glucuronoxylans represent a large group of naturally occurring and renewable biopolymers with a wide range of application possibilities. Controlled depolymerization of Fagus sylvatica 4‐ O ‐methylglucuronoxylan afforded three fractions of descending molecular mass, i.e ., 3000, 2600, and 1800 g/mol. The native polymer (GX1) and its depolymerized fractions (GX2, GX3, and GX4) were decorated by functional groups to give sulfated products (GXS1, GXS2, GXS3, and GXS4) which were used for pharmacological tests. Antitussive activity tests revealed that the increase in the dose of the glucuronoxylan sulfate (GXS1) from 50 to 100 mg/kg body weight resulted in only slightly increased cough‐suppressing effect. This fact indicates that the cough‐suppressing effect of the glucuronoxylan sulfate is not dose dependent. Results have shown significant cough‐suppressing effect of GXS1, it was only slightly lower than the effect of narcotic codeine. Glucuronoxylan‐derived fractions decorated by sulfates (GXS2, GXS3, and GXS4) showed similar cough‐suppressing effect as the polymer‐sulfate (GXS1) confirming thus that the changes in molecular mass does not affect the cough suppressive activity. Similarly, different contents of sulfate groups in GXS2, GXS3, and GXS4 did not influence their effect. Tests have shown that in the antitussive activity of all glucuronoxylan sulfates a bronchodilation was not involved. During the experiment course, no serious side effects after administration of glucuronoxylan sulfates were observed which is important fact from the application point of view.
Romidepsin and Belinostat Synergize the Antineoplastic Effect of Bortezomib in Mantle Cell Lymphoma (2010)

Collectively, these data strongly suggest that HDACI such as romidepsin or belinostat in combination with a proteasome inhibitor could represent a novel and rationale platform for the treatment of MCL.
Chicken TLR21 Is an Innate CpG DNA Receptor Distinct from Mammalian TLR9 (2010)

TLRs comprise a family of evolutionary conserved sensory receptors that respond to distinct classes of ligands. For one major evolutionary branch of TLRs, the ligands are still largely unknown. Here we report the cloning and function of one member of this group, chicken TLR21 (chTLR21). This TLR is absent in the human species but has homologs in fish and frog and displays similarity with mouse TLR13. Expression of chTLR21 in HEK293 cells resulted in activation of NF-kappaB in response to unmethylated CpG DNA, typically recognized by mammalian TLR9. Silencing of chTLR21 (but not chTLR4) in chicken macrophages inhibited the response to CpG-DNA (but not to LPS), indicating similar functionality of the endogenous receptor. ChTLR21 responded to human- and murine-specific TLR9 ligands, as well as to bacterial genomic DNA isolated from Salmonella enterica serovar Enteritidis. Confocal microscopy located chTLR21 in the same intracellular compartments as human TLR9. Inhibition of the chTLR21 response by the endosomal maturation inhibitor chloroquine suggested that the receptor is functional in endolysosomes, as known for TLR9. The analogous localization and function of the phylogenetically only distantly related chTLR21 and mammalian TLR9 suggest that during evolution different classes of TLRs have emerged that recognize the same type of ligands.
Thioridazine, an antipsychotic drug, elicits potent antitumor effects in gastric cancer (2014)

Thioridazine, an antipsychotic drug, has been reported to induce apoptosis in various types of cancer cells, with specificity on targeting cancer stem cells (CSCs). However, whether it elicits anticancer effects in gastric cancer has never been reported. In the present study, we examined the ability of thioridazine to induce cell death in the gastric cancer cell lines NCI-N87 and AGS, and detected its in vivo tumor inhibition capacity. Thioridazine elicited cytotoxic effects on NCI-N87 and AGS cells in a dose-dependent manner, and inhibited the colony formation abilitiy of the NCI-N87 and AGS cells. Thioridazine treatment induced nuclear fragmentation, increased the proportion of sub-G1 phase cells, and elevated the percentage of Annexin V-positive cells, suggesting the occurrence of apoptosis. Moreover, thioridazine induced gastric cancer cell apoptosis in a caspase-dependent manner, as shown by a decrease in the precursors of casapse-9, caspase-8 and caspase-3, and by the ability of the caspase inhibitor Z-VAD-FMK to reverse the cytotoxic effect of thioridazine. JC-1 staining further revealed that thioridazine induced gastric cancer cell apoptosis via the mitochondrial pathway. In addition, thioridazine pretreatment inhibited the growth of NCI-N87 cell-derived tumors. The present study demonstrated that the antipsychotic drug thioridazine possesses anti-gastric cancer ability through in vitro and in vivo experiments, suggesting thioridazine as a potential drug in gastric cancer therapy.
Optimized substrate concentrations for production of long-chain isomaltooligosaccharides using dextransucrase of Leuconostoc mesenteroides B-512F. (2008)

Isomaltooligosaccharide (IMO) is a promising dietary component with prebiotic effect, and the long-chain IMOs are preferred to short chain ones owing to the longer persistence in the colon. To establish the optimal process for synthesis of long-chain IMOs, we systematically examined the reaction condition of dextransucrase of Leuconostoc mesenteroides B-512F by changing the ratio of sucrose to maltose (varying as 1:4, 1:2, 1:1, and 2:1) and amount of each sugar (from 2% to 20%). As a result, a ratio of 2:1 (sucrose to maltose, 10:5% or 20:10%, w/v) was determined as an optimal condition for long-chain IMO synthesis (DP3-DP9) with relatively higher yields (70-90%, respectively).
Defective Retinal Vascular Endothelial Cell Development As a Consequence of Impaired Integrin αVβ8-Mediated Activation of Transforming Growth Factor-β (2012)

Deletions of the genes encoding the integrin αVβ8 (Itgav, Itgb8) have been shown to result in abnormal vascular development in the CNS, including prenatal and perinatal hemorrhage. Other work has indicated that a major function of this integrin in vivo is to promote TGFβ activation. In this paper, we show that Itgb8 mRNA is strongly expressed in murine Müller glia and retinal ganglion cells, but not astrocytes. We further show that Itgb8 deletion in the entire retina severely perturbs development of the murine retinal vasculature, elevating vascular branch point density and vascular coverage in the superficial vascular plexus, while severely impairing formation of the deep vascular plexus. The stability of the mutant vasculature is also impaired as assessed by the presence of hemorrhage and vascular basal lamina sleeves lacking endothelial cells. Specific deletion of Itgb8 in Müller glia and neurons, but not deletion in astrocytes, recapitulates the phenotype observed following Itgb8 in the entire retina. Consistent with αVβ8's role in TGFβ1 activation, we show that retinal deletion of Tgfb1 results in very similar retinal vascular abnormalities. The vascular deficits appear to reflect impaired TGFβ signaling in vascular endothelial cells because retinal deletion of Itgb8 reduces phospho-SMAD3 in endothelial cells and endothelial cell-specific deletion of the TGFβRII gene recapitulates the major deficits observed in the Itgb8 and TGFβ1 mutants. Of special interest, the retinal vascular phenotypes observed in each mutant are remarkably similar to those of others following inhibition of neuropilin-1, a receptor previously implicated in TGFβ activation and signaling.
Reconstitution of immunity to adenovirus after pediatric bone marrow transplant (2005)

Adenovirus has been shown to be a significant cause of morbidity, and mortality in the pediatric hematopoietic stem cell transplant (HSCT) patient. The degree of immune suppression appears to be the most important risk factor for development of serious adenoviral disease. While withdrawal of immune suppression, and the use of cidofovir may have some effect in reducing viral load and hastening immune recovery, these approaches have appreciable side effects and are not always effective. Little is known about the reconstitution of immunity to adenovirus after HSCT. Therefore, in this current study we have prospectively monitored the recovery of adenovirus cellular immunity in pediatric HSCT patients receiving matched-related, mismatched related or unrelated donor grafts. 23 pediatric HSCT patients (age range 14 months-20 years) were enrolled on this study which aims to monitor viral load and recovery of cellular immunity to adenovirus post HSCT. We have developed and validated a real-time PCR (Q-PCR) to obtain a quantitative measure of viral load. Q-PCR is more sensitive than semi-quantitative PCR and shows that adenovirus can be detected (despite the absence of symptoms) in the blood, stool or urine at rates of up to 70%. 22 patients have >30 days follow-up (mean 147 days, range 60–240 days). 18/22 (81%) have had detectable levels of adenoviral DNA in stool (14/18) or blood (13/18). Positivity in the stool usually preceded adenovirus detection in the blood. 3 patients were exclusively positive in the blood on one occasion with low viral copy number (range 650 to 1200 copies/ml). 8 patients have had multiple blood samples positive for adenovirus DNA ranging in peak viral copy concentration from 1200 to 92500 cp/ml (mean= 31056 cp/ml). Peak copy number in the stool ranged from 1× 103 to 9× 109 cp/gram stool. In a preliminary analysis rising levels appear to correlate with risk of infection. ELISPOT assay and tetramer analysis for known HLA-restricted adenovirus epitopes will be used to monitor recovery of adenovirus specific T-cells in these patients. The results from this study will, therefore provide critical information for our forthcoming clinical trial where we will evaluate if immunity to adenovirus can be improved by adoptive transfer of adenovirus specific CTLs generated by culture with monocytes transduced with an Ad5/35 adenoviral vector (Leen et al, Blood 2004;104:2432–40).
Sucrose octasulfate regulates fibroblast growth factor‐2 binding, transport, and activity: Potential for regulation of tumor growth (2007)

The antithrombotic activity of heparin has largely been credited with the success found in some cancer treatment by heparin. There are, however, many potent growth factors involved in tumor and blood vessel growth that bind to heparin with high affinity and their regulation by heparin may play a role in heparin's efficacy. We therefore chose to study the activity of a heparin analog, sucrose octasulfate (SOS), which has been similarly shown to interact with heparin-binding growth factors. Using mouse melanoma and lung carcinoma models, we demonstrate in vivo inhibition of tumor growth by SOS. SOS, however, showed little effect in coagulation assays indicating that this activity was not a primary mechanism of action for this molecule. Studies were then performed to assess the effect of SOS on basic fibroblast growth factor (FGF-2) activity, a growth factor which promotes tumor and blood vessel growth and is produced by B16 melanoma cells. SOS potently inhibited FGF-2 binding to endothelial cells and stripped pre-bound FGF-2 from cells. SOS also regulated FGF-2 stimulated proliferation. Further, SOS facilitated FGF-2 diffusion through Descemet's membrane, a heparan sulfate-rich basement membrane from the cornea, suggesting a possible role in FGF-2 clearance. Our results suggest that molecules such as SOS have the potential to remove growth factors from tumor microenvironments and the approach offers an attractive area for further study.
Species and genus level resolution analysis of gut microbiota in Clostridium difficile patients following fecal microbiota transplantation (2014)

We conclude that C. difficile infection can be successfully treated by fecal microbiota transplantation and that this leads to stable transformation of the distal gut microbial community from the one abundant in aerotolerant species to that dominated by members of the Clostridia.
Within-patient consistency of response of rizatriptan for treating migraine (2000)

The response to 10 mg of oral rizatriptan within individual patients was consistent over three attacks on a range of measures.