gebhart/patrepeval huggingface dataset:
A locus regulating bronchial hyperresponsiveness maps to chromosome 5q (1994)

Bronchial hyperresponsiveness (BHR) is one of the hallmarks of asthma. BHR correlates well with asthmatic symptoms and the response to treatment. Moreover, BHR appears to be closely related to airways inflammation. Numerous studies have demonstrated a familial aggregation; however, this phenotype is not likely inherited as a simple Mendelian trait. BHR is also closely associated with total serum IgE levels, as are allergy and asthma. We studied 92 families from Northern Holland ascertained through a parent with asthma who were originally studied between 1962-1970. Since there are a number of candidate genes on chromosome 5q potentially important in producing BHR, families were genotyped for markers in this region. These genes regulate IgE production and the cellular elements that are likely involved in inflammation associated with BHR, allergy and asthma. They include IL-4, IL-3, IL-5, IL-9, IL-12, IL-13 and GM-CSF. Linkage of BHR with markers on 5q was tested using a model free sib-pair method. The data suggest a locus for BHR maps near the cytokine gene cluster on 5q. This region appears critical in producing susceptibility to BHR and possibly to asthma.
Highly purified human-derived follicle-stimulating hormone (Bravelle®) has equivalent efficacy to follitropin-beta (Follistim ®) in infertile women undergoing in vitro fertilization (2003)

Bravelle and Follistim had comparable efficacy in controlled ovarian hyperstimulation in women undergoing IVF-ET. There were no differences in the nature or number of adverse events between the treatment groups although Bravelle injections were reported to be significantly less painful.
Multiport network description and radiation characteristics of coupled dielectric resonator antennas (1998)

An efficient procedure is presented to investigate the mutual coupling effects and radiation characteristics of dielectric resonator (DR) antennas operating in an array environment. The procedure is based on the method of moments (MoM) as applied to a system of surface integral equations (SIEs) for the coupling of a dielectric body of revolution (BOR) to a nonBOR geometry. The antenna array elements are situated on a ground plane and fed by coaxial probes. Multiport network impedance parameters computed by this method show good agreement with those obtained by measurement. Computed driving point impedances are given for arrays exhibiting optimum pattern performance in terms of low cross polarization and good pattern symmetry.
Radiofrequency catheter ablation for the treatment of human type 1 atrial flutter. Identification of a critical zone in the reentrant circuit by endocardial mapping techniques. (1992)

1) Radiofrequency energy applied to a critical area in the atrial flutter reentrant circuit, inferior or posterior to the coronary sinus ostium, will terminate and prevent arrhythmia reinduction. 2) Long-term follow-up in a larger series of patients will be required to confirm efficacy of this technique, although short-term results look promising.
Altering the Reaction Specificity of Eukaryotic Ornithine Decarboxylase, (2000)

Ornithine decarboxylase (ODC) catalyzes the first committed step in the biosynthesis of polyamines, and it has been identified as a drug target for the treatment of African sleeping sickness, caused by Trypanosoma brucei. ODC is a pyridoxal 5'-phosphate (PLP) dependent enzyme and an obligate homodimer. X-ray structural analysis of the complex of the T. brucei wild-type enzyme with the product putrescine reveals two structural changes that occur upon ligand binding: Lys-69 is displaced by putrescine and forms new interactions with Glu-94 and Asp-88, and the side chain of Cys-360 rotates into the active site to within 3.4 A of the imine bond. Mutation of Cys-360 to Ala or Ser reduces the k(cat) of the decarboxylation reaction by 50- and 1000-fold, respectively. However, HPLC analysis of the products demonstrates that the mutant enzymes almost exclusively catalyze a decarboxylation-dependent transamination reaction to form pyridoxamine 5-phosphate (PMP) and gamma-aminobutyraldehyde, instead of PLP and putrescine. This side reaction arises when the decarboxylated substrate intermediate is protonated at C4' of PLP instead of at the C(alpha) of substrate. For the reaction catalyzed by the wild-type enzyme, this side reaction occurs infrequently (<0.01% of the turnovers). Single turnover analysis and multiwavelength stopped-flow spectroscopic studies suggest that for the mutant ODCs protonation at C4' occurs either very rapidly or in a concerted reaction with decarboxylation and that the rate-limiting step in the steady-state reaction is Schiff base hydrolysis/product release. These studies demonstrate a role for Cys-360 in the control of the C(alpha) protonation step that catalyzes the formation of the physiological product putrescine. The results further provide insight into the mechanism by which this class of PLP-dependent enzymes controls reaction specificity.
Retroviral vectors (2000)

Traditionally, the retrovirus is regarded as an enemy to be overcome. However, for the past two decades retroviruses have been harnessed as vehicles for transferring genes into eukaryotic cells, a process known as transduction. During this time, the technology has moved from being a scientific laboratory tool to a potential clinical molecular medicine to be used in gene therapy. This review explains the strategy for harnessing the retrovirus life cycle, the scientific research and clinical applications of this methodology, and its limitations, as well as possible future developments.
Characterization of a bovine synovial fluid lubricating factor. II. Comparison with purified ocular and salivary mucin (1992)

Boundary lubricating activity and biochemical characteristics of purified lubricating factor from bovine synovial fluid (PSLF) were compared to those of mucinous glycoprotein from human submandibular saliva and stimulated tears. Mammalian synovial fluid and saliva contain mucinous glycoproteins which reduce the coefficient of friction (mu) in a bearing of latex:glass which isolates boundary lubrication. In contrast, mucin secreted by the lacrimal gland did not lubricate. Cleveland plotting showed that these species are not identical.
Hepatorenal syndrome (2012)

Hepatorenal syndrome (HRS) is defined as a functional renal failure in patients with liver disease with portal hypertension and it constitutes the climax of systemic circulatory changes associated with portal hypertension. This term refers to a precisely specified syndrome featuring in particular morphologically intact kidneys, where regulatory mechanisms have minimised glomerular filtration and maximised tubular resorption and urine concentration, which ultimately results in uraemia. The syndrome occurs almost exclusively in patients with ascites. Type 1 HRS develops as a consequence of a severe reduction of effective circulating volume due to both an extreme splanchnic arterial vasodilatation and a reduction of cardiac output. Type 2 HRS is characterised by a stable or slowly progressive renal failure so that its main clinical consequence is not acute renal failure, but refractory ascites, and its impact on prognosis is less negative. Liver transplantation is the most appropriate therapeutic method, nevertheless, only a few patients can receive it. The most suitable "bridge treatments" or treatment for patients ineligible for a liver transplant include terlipressin plus albumin. Terlipressin is at an initial dose of 0.5-1 mg every 4 h by intravenous bolus to 3 mg every 4 h in cases when there is no response. Renal function recovery can be achieved in less than 50% of patients and a considerable decrease in renal function may reoccur even in patients who have been responding to therapy over the short term. Transjugular intrahepatic portosystemic shunt plays only a marginal role in the treatment of HRS.
Biarylcarboxylic Acids and -amides:  Inhibition of Phosphodiesterase Type IV versus [3H]Rolipram Binding Activity and Their Relationship to Emetic Behavior in the Ferret (1996)

In addition to having desirable inhibitory effects on inflammation, anaphylaxis, and smooth muscle contraction, PDE-IV inhibitors also produce undesirable side effects including nausea and vomiting. In general, compounds that inhibit PDE-IV also potently displace [3H]rolipram from a high-affinity binding site in rat cortex. While this binding site has not been identified, it has been proposed to be an allosteric binding site on the PDE-IV enzyme. Preliminary studies have suggested that the emetic potency of PDE-IV inhibitors is correlated with affinity for the brain rolipram binding site rather than potency at inhibiting PDE-IV enzyme activity. Efforts to eliminate the emetic potential of PDE-IV inhibitors were directed toward developing compounds with decreased [3H]rolipram binding affinity while retaining PDE-IV potency. Thus, a novel series of 4-(3-alkoxy-4-methoxyphenyl)benzoic acids and their corresponding carboxamides were prepared and evaluated for their PDE-IV inhibitory and rolipram binding site properties. Modification of the catechol ether moiety led to phenylbutoxy and phenylpentoxy analogues that provided the desired activity profile. Specifically, 4-[3-(5-phenylpentoxy)-4-methoxyphenyl]-2-methylbenzoic acid, 18, was found to exhibit potent PDE-IV inhibitory activity (IC50 0.41 microM) and possessed 400 times weaker activity than rolipram for the [3H]rolipram binding site. In vivo, compound 18 was efficacious in the guinea pig aerosolized antigen induced airway obstruction assay (ED50 8.8 mg/kg, po) and demonstrated a significant reduction in emetic side effects (ferret, 20% emesis at 30 mg/kg, po).
Basic fibroblast growth factor causes growth arrest in MCF-7 human breast cancer cells while inducing both mitogenic and inhibitory G1 events. (1997)

Basic fibroblast growth factor (bFGF), a classical mitogen in fibroblasts and endothelial cells, inhibits the proliferation of MCF-7 and other human breast cancer cell lines. To explain this paradoxic effect, we investigated the effects of bFGF on cyclins and protein members of cyclin complexes that exert positive and negative control on the progression of cells through the G1 phase of the cell cycle. bFGF induced an increase in cyclin D1, cyclin E, and cyclin-dependent kinase 4 (cdk4) protein levels in a bFGF dose-dependent manner. However, bFGF also induced a heat-stable, transferable cytoplasmic factor in MCF-7 cells that inhibited the histone H1 kinase activity of reconstituted cyclin E-cdk2 and cyclin A-cdk2 complexes from Mv1Lu mink lung epithelial cells. The appearance of this inhibitor correlated with a bFGF dose- and time-dependent increase in the levels of cdk inhibitor p21(WAF1/CIP1) mRNA and protein. The increase in the level of p21(WAF1/CIP1) was associated with the disappearance of the rapidly migrating, activated form of cdk2 from cell lysates, dephosphorylation of the retinoblastoma protein (Rb), and a decrease in cyclin A levels. These changes were represented in the cyclin D1 and E complexes by an increased association with p21(WAF1/CIP1), proliferating cell nuclear antigen (PCNA), and the inactive form of cdk2, without an absolute change in cellular PCNA levels and by a switch in the association of cyclin D1 complexes with the hyperphosphorylated form to the dephosphorylated form of Rb. These experiments demonstrate that stimulation of MCF-7 cells with bFGF, although resulting in up-regulation of G1 proteins responsible for mitogenic events, also induces a concomitant decrease in cyclin A levels and an increase in p21(WAF1/CIP1) mRNA and protein and results in inactivation of cdk2, dephosphorylation of Rb, and a segregation of PCNA to the G1 cyclin complexes. The dual, conflicting signaling by bFGF results in a net inhibitory phenotype in these cells. These experiments suggest a pleiotropic role for bFGF in breast cancer.
High-Contrast Electrochromism from Layer-By-Layer Polymer Films (2003)

Layer-by-layer (LBL) assembly is the ideal processing technique to combine two electrochromic polymers into a single thin film composite with fine control over morphology and composition. Here we present a very-high-contrast electrochromic composite developed from the LBL assembly of two readily available cathodically coloring electrochromic polymers: poly(hexyl viologen) (PXV) and the poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:SPS) colloid. Characterization of assembly reveals that film thickness increases exponentially with increasing layer-pair number, seemingly due to the globular nature of the PEDOT:SPS colloid. Elemental analysis confirmed the presence of both polymers in the final film and allowed the determination of a bulk composition profile. In detailed electrochemical and spectral investigations, the “dual electrochrome” was compared to single-electrochrome LBL films, confirming that both polymers contribute to electrochromic switching. Due to the unusual film architecture and complex interactions between PXV and PEDOT, a charge-trapping system is formed within the layers, resulting in a type of electrochemical rectification. The performance of PXV/PEDOT:SPS as a material for electrochromic applications was extremely competitive, with color-change response times ranging from 1 to 4 s and high contrast between a transmissive oxidized state and a deep purple/blue reduced state. The LBL approach was used to optimize the thickness of the polymer film, and a 45-layer pair PXV/PEDOT:SPS film was found to exhibit a transmittance change of 82.1% at 525 nm, one of the highest reported contrasts in polymer electrochromics. These results demonstrate the power of the LBL processing technique to create new electroactive materials with both unusual properties and unequalled potential for application. Future directions are illuminated for the LBL development of multiply colored, fast switching, and high contrast electrochromic materials from cheap and readily available electrochromic polyions.
Transfer RNA genes frequently serve as integration sites for prokaryotic genetic elements (1989)

The DNA sequences were determined at the boundaries of the integrated copy of the archaebacterial genetic element SSV1. A 44 bp sequence present as a single copy on the 15.5 kb circular SSV1 DNA flanked the integrated copy as a direct DNA sequence repeat, suggesting that SSV1 integration occurred by recombination between this 44 bp SSV1 sequence and an identical sequence on the bacterial chromosome. At the left attachment site, a region encompassing the 44 bp attachment core sequence and the 31 nucleotides upstream of it displayed all characteristics expected for an arginine tRNA gene. An analysis of published attachment site sequences of other systems revealed that tRNA genes also constitute the bacterial attachment site in the case of three temperate phages and two transmissible plasmids in eubacteria, indicating a widespread occurrence of tRNA genes as integration target sites. This finding may be important for the understanding of mechanisms and evolution of site-specific recombination.
E7080 (lenvatinib) in addition to best supportive care (BSC) versus BSC alone in third-line or greater nonsquamous, non-small cell lung cancer (NSCLC). (2014)

8043 Background: Lenvatinib (E7080; LEN) is an oral, tyrosine kinase inhibitor targeting VEGFR1-3, FGFR1-4, RET, KIT, and PDGFRβ with evidence of antitumor activity in a broad range of solid tumors. Currently there is an unmet medical need for treatments in third-line or greater NSCLC patients (pts). Methods: This study was a double-blind, placebo-controlled, multicenter, randomized Phase II study of LEN 24 mg PO once daily + BSC vs. placebo (PBO) + BSC (2:1 randomization). Pts with nonsquamous NSCLC who had failed ≥ 2 two systemic anticancer regimens were enrolled. Prior erlotinib or gefitinib was required for pts with known EGFR-activating mutations. The primary endpoint was overall survival (OS). Progression free survival (PFS), overall response rate (ORR), and disease control rate (DCR) were based on investigator assessment. Efficacy endpoints were estimated via Kaplan-Meier. Results: 135 pts enrolled in the study. Per protocol, the study was unblinded and analyzed after 90 deaths. 76% received ≥ 3 prior anti-cancer regimens and 85% received prior erlotinib or gefitinib (similar rates in each arm). A summary of efficacy and safety is presented by study arm (Table). In a post hoc analysis, a similar treatment effect was observed among subjects with wild-type EGFR. Conclusions: LEN in addition to BSC demonstrated a clinically meaningful improvement in both OS and PFS (~ 3 months) in heavily pretreated patients with NSCLC, including those who received prior EGFR inhibitors. LEN was generally well-tolerated, with an AE profile consistent with observed LEN monotherapy studies. These data warrant additional evaluation of LEN in this population. Clinical trial information: NCT01529112. Median value or percentage LEN + BSC (n=89) PBO + BSC (n=46) P value OS, wks (95% CI) 38.4 (26.57, 47.86) N=58 events 24.1 (15.29, 36.43) N=37 events p = 0.065 PFS, weeks (95% CI) 20.9 (15.86, 23.86) N=73 events 7.9 (7.43, 8.14) N=45 events p < 0.001 ORR 10.1% 2.2% 0.1635 DCR 42.7% 19.6% 0.0079 Treatment duration (days) 113 58 Not compared (NC) Serious adverse events (AEs) 52% 46% NC Grade 3/grade 4 AEs: Hypertension Dyspnea Pneumonia 69% 17% 9% 9% 50% 0% 13% 6.5% NC Study discontinuation due to AE 24.7% 17.4% NC
Effect of wetting on capillary pumping in microchannels (2013)

We investigate capillary pumping in microchannels both experimentally and numerically. Putting two droplets of different sizes at the in/outlet of a microchannel, there will in general be a flow from the smaller droplet to the larger one due to the Laplace pressure difference. We show that an unusual flow from a larger droplet into a smaller one is possible by manipulating the wetting properties, notably the contact line pinning. In addition, we propose a way to actively control the flow by electrowetting.
Sequencing technologies and genome sequencing (2011)

The high-throughput - next generation sequencing (HT-NGS) technologies are currently the hottest topic in the field of human and animals genomics researches, which can produce over 100 times more data compared to the most sophisticated capillary sequencers based on the Sanger method. With the ongoing developments of high throughput sequencing machines and advancement of modern bioinformatics tools at unprecedented pace, the target goal of sequencing individual genomes of living organism at a cost of $1,000 each is seemed to be realistically feasible in the near future. In the relatively short time frame since 2005, the HT-NGS technologies are revolutionizing the human and animal genome researches by analysis of chromatin immunoprecipitation coupled to DNA microarray (ChIP-chip) or sequencing (ChIP-seq), RNA sequencing (RNA-seq), whole genome genotyping, genome wide structural variation, de novo assembling and re-assembling of genome, mutation detection and carrier screening, detection of inherited disorders and complex human diseases, DNA library preparation, paired ends and genomic captures, sequencing of mitochondrial genome and personal genomics. In this review, we addressed the important features of HT-NGS like, first generation DNA sequencers, birth of HT-NGS, second generation HT-NGS platforms, third generation HT-NGS platforms: including single molecule Heliscope™, SMRT™ and RNAP sequencers, Nanopore, Archon Genomics X PRIZE foundation, comparison of second and third HT-NGS platforms, applications, advances and future perspectives of sequencing technologies on human and animal genome research.
Effect of zeta potential of cationic liposomes containing cationic cholesterol derivatives on gene transfection (1996)

Cationic liposomes are known to be useful tools for gene transfection. However, the relation between transfection efficiency and physicochemical properties of liposomes has not been well understood. Here, we synthesized eight cationic derivatives of cholesterol which contain a tertiary amino head group with a different spacer arm. Transfection of plasmid pSV2CAT DNA into cells was done by cationic liposomes made of a mixture of dioleoylphosphatidylethanolamine (DOPE) and each cationic cholesterol derivative. At the same time we measured zeta potential of cationic liposomes by laser Doppler spectroscopy. The present results indicated that zeta potentials of cationic liposomes were well related to transfection activity of pSV2CAT DNA. This suggested that zeta potential of cationic liposomes is one of important factors which control gene transfection.
A biphasic pattern of gene expression during mouse retina development (2006)

This study provides a complementary genome-wide view of common gene dynamics and a broad molecular classification of mouse retina development. Different genes in the same functional clusters are expressed in the different developmental stages, suggesting that cells might change gene expression profiles from differentiation to maturation stages. We propose that large-scale changes in gene regulation during development are necessary for the final maturation and function of the retina.
Autocrine Nitric Oxide Modulates CD95-induced Apoptosis in γδ T Lymphocytes (1997)

Gammadelta T lymphocytes play an important early role in the defense against pathogens. Their function is terminated by acquisition of susceptibility to CD95-triggered apoptosis. Here we show that the regulation of this process depends on the activity of the endothelial NO synthase expressed by gammadelta T lymphocytes, which is modulated in an activation-dependent way. The effects of nitric oxide thus generated, mediated via cGMP generation, are exerted at at least two sites along the CD95 signaling cascade: one at, or upstream, and the other downstream of ceramide generation. At either site, nitric oxide/cGMP action is sufficient for protection from apoptosis. The effect of NO is selective for apoptosis induced by CD95 cross-linking, since it does not affect apoptotic program triggered by other stimuli. The evidence here reported demonstrates a new physiological role for nitric oxide, acting as a survival factor for T lymphocytes.
Monoclonal antibody-dependent murine macrophage-mediated cytotoxicity against human tumors is stimulated by lentinan. (1985)

The beta (1----3) glucan lentinan was tested for its capacity to increase the cytotoxic effect of murine peritoneal macrophages for human tumor cells in the presence of monoclonal antibodies (MAbs). Activity was maximum in macrophages obtained on day 5 following intraperitoneal injection of CBA mice with 2.5 mg of lentinan per kg body weight. Macrophages stimulated by lentinan were cytotoxic in conjunction with IgG1, IgG2a and IgG3 MAbs, but not with IgG2b, IgM, or IgA MAbs. The demonstration of a similar enhancing effect by lentinan on human macrophages might have implications for potentiating the tumoricidal effect of these macrophages in the presence of tumor antigen-specific MAbs.