gebhart/patrepeval huggingface dataset:
Enterobacterial 38-kDa outer membrane protein is an age-dependent molecular marker of innate immunity and immunoglobulin deficiency as results from its reactivity with IgG and IgA antibody (2006)

In earlier studies on an animal model we observed protective properties of outer membrane proteins (OMPs) of Shigella, Hafnia, and Escherichia coli strains. In order to investigate human sera for reactivity with OMPs we subjected these proteins to immunoblotting with umbilical cord plasma and sera from children and adults. The IgG and IgA antibodies interacted primarily with a 38-kDa protein, in similar way for several enterobacterial strains, but different for Pseudomonas aeruginosa. This observation prompted us to determine the reactivity with the purified 38-kDa OMP in the sera of several groups of children. The reactivity of the protein from Shigella flexneri serotype 3a with sera in ELISA was age dependent, increasing from low reactivity in infants to the adult antibody level. The IgG and IgA antibody specific response thus revealed the normal pattern of immunity. The level of IgA and IgG antibody was significantly low in child patients with IgA and/or IgG immunoglobulin deficiencies, but was at the healthy control level in children with recurrent respiratory tract inflammation. These data correlated with total IgA and IgG levels in immunoglobulin-deficient children. The results indicate that this protein may serve as an immunodiagnostic marker, but also as an antigen carrier in vaccines.
Diminished Amyloid-β Burden in Tg2576 Mice Following a Prophylactic Oral Immunization with a Salmonella-Based Amyloid-β Derivative Vaccine (2009)

Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. Prior to the side effects in the first Elan/Wyeth AD vaccine trial, we proposed using amyloid-beta (Abeta) derivatives as a safer approach. The route of administration may also affect vaccine safety. To assess the feasibility of oral immunization that promotes mucosal immunity, Tg2576 AD model mice were treated prophylactically three times over 6 weeks starting at 3-5 months of age with a Salmonella vaccine expressing K6Abeta(1-30). At 22-24 months of age, cortical Abeta plaque burden and total Abeta(40/42) levels were reduced by 48-75% in the immunized mice compared to controls, which received unmodified Salmonella. Plaque clearance was not associated with increased microglial activation, which may be explained by the long treatment period. Furthermore, cerebral microhemorrhages were not increased in the treated mice in contrast to several passive Abeta antibody studies. These results further support our findings with this immunogen delivered subcutaneously and demonstrate its efficacy when given orally, which may provide added benefits for human use.
The Top 10 Mud-Related Concerns in Deepwater Drilling Operations (2000)

Abstract The deepwater environment can place serious demands and constraints on the drilling fluid during well construction. Failure to adequately address these concerns can lead to excessive well costs, unscheduled trouble time, unnecessary high-risk activities, and poor performance. In this paper, we identify and succinctly discuss the top 10 mud-related concerns based on field experience in the Gulf of Mexico, off-shore West Africa, Southeast Asia, and Brazil. Mud-related concerns selected for this top-10 list are (1) lost circulation, (2) mud properties, (3) solids transport, (4) stuck pipe, (5) wellbore stability, (6) shallow hazards, (7) gas hydrates, (8) reservoir productivity, (9) environmental issues, and (10) fluid-related logistics.
Disruption of the glucosylceramide biosynthetic pathway in Aspergillus nidulans and Aspergillus fumigatus by inhibitors of UDP‐Glc:ceramide glucosyltransferase strongly affects spore germination, cell cycle, and hyphal growth (2002)

The opportunistic mycopathogen Aspergillus fumigatus expresses both glucosylceramide and galactosylceramide (GlcCer and GalCer), but their functional significance in Aspergillus species is unknown. We here identified and characterized a GlcCer from Aspergillus nidulans, a non-pathogenic model fungus. Involvement of GlcCer in fungal development was tested on both species using a family of compounds known to inhibit GlcCer synthase in mammals. Two analogs, D-threo-1-phenyl-2-palmitoyl-3-pyrrolidinopropanol (P4) and D-threo-3',4'-ethylenedioxy-P4, strongly inhibited germination and hyphal growth. Neutral lipids from A. fumigatus cultured in the presence of these inhibitors displayed a significantly reduced GlcCer/GalCer ratio. These results suggest that synthesis of GlcCer is essential for normal development of A. fumigatus and A. nidulans.
Current Topics in RNA−Protein Recognition:  Control of Specificity and Biological Function through Induced Fit and Conformational Capture (2001)

ADVERTISEMENT RETURN TO ISSUECurrent Topics/Persp...Current Topics/PerspectivesNEXTCurrent Topics in RNA−Protein Recognition: Control of Specificity and Biological Function through Induced Fit and Conformational Capture†Nicolas Leulliot and Gabriele VaraniView Author Information MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 2QH, England Cite this: Biochemistry 2001, 40, 27, 7947–7956Publication Date (Web):June 13, 2001Publication History Received4 April 2001Revised4 May 2001Published online13 June 2001Published inissue 1 July 2001https://pubs.acs.org/doi/10.1021/bi010680yhttps://doi.org/10.1021/bi010680yreview-articleACS PublicationsCopyright © 2001 American Chemical SocietyRequest reuse permissionsArticle Views1823Altmetric-Citations280LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-Alertsclose SUBJECTS:Conformation,Genetics,Interfaces,Nucleic acid structure,Peptides and proteins Get e-Alerts
The Herpes Simplex Virus US11 Protein Effectively Compensates for the γ134.5 Gene if Present before Activation of Protein Kinase R by Precluding Its Phosphorylation and That of the α Subunit of Eukaryotic Translation Initiation Factor 2 (1998)

In herpes simplex virus-infected cells, viral gamma134.5 protein blocks the shutoff of protein synthesis by activated protein kinase R (PKR) by directing the protein phosphatase 1alpha to dephosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2alpha). The amino acid sequence of the gamma134.5 protein which interacts with the phosphatase has high homology to a domain of the eukaryotic protein GADD34. A class of compensatory mutants characterized by a deletion which results in the juxtaposition of the alpha47 promoter next to US11, a gamma2 (late) gene in wild-type virus-infected cells, has been described. In cells infected with these mutants, protein synthesis continues even in the absence of the gamma134.5 gene. In these cells, PKR is activated but eIF-2alpha is not phosphorylated, and the phosphatase is not redirected to dephosphorylate eIF-2alpha. We report the following: (i) in cells infected with these mutants, US11 protein was made early in infection; (ii) US11 protein bound PKR and was phosphorylated; (iii) in in vitro assays, US11 blocked the phosphorylation of eIF-2alpha by PKR activated by poly(I-C); and (iv) US11 was more effective if present in the reaction mixture during the activation of PKR than if added after PKR had been activated by poly(I-C). We conclude the following: (i) in cells infected with the compensatory mutants, US11 made early in infection binds to PKR and precludes the phosphorylation of eIF-2alpha, whereas US11 driven by its natural promoter and expressed late in infection is ineffective; and (ii) activation of PKR by double-stranded RNA is a common impediment countered by most viruses by different mechanisms. The gamma134.5 gene is not highly conserved among herpesviruses. A likely scenario is that acquisition by a progenitor of herpes simplex virus of a portion of the cellular GADD34 gene resulted in a more potent and reliable means of curbing the effects of activated PKR. US11 was retained as a gamma2 gene because, like many viral proteins, it has multiple functions.
A Compact Functional Quantum Dot−DNA Conjugate:  Preparation, Hybridization, and Specific Label-Free DNA Detection (2008)

In this letter, we report the preparation of a compact, functional quantum dot (QD)-DNA conjugate, where the capturing target DNA is directly and covalently coupled to the QD surface. This enables control of the separation distance between the QD donor and dye acceptor to within the range of the Förster radius. Moreover, a tri(ethylene glycol) linker is introduced to the QD surface coating to effectively eliminate the strong, nonspecific adsorption of DNA on the QD surface. As a result, this QD-DNA conjugate hybridizes specifically to its complementary DNA with a hybridization rate constant comparable to that of free DNAs in solution. We show this system is capable of specific detection of nanomolar unlabeled complimentary DNA at low DNA probe/QD copy numbers via a "signal-on" fluorescence resonance energy transfer (FRET) response.
Requirement for Leptin in the Induction and Progression of Autoimmune Encephalomyelitis (2001)

Recent evidence indicates that leptin modifies T cell immunity, and may provide a key link between nutritional deficiency and immune dysfunction. To study the influence of leptin on autoimmunity, susceptibility to experimental autoimmune encephalomyelitis induced by immunization with a myelin-derived peptide was examined in leptin-deficient, C57BL/6J-ob/ob mice, with or without leptin replacement, and in wild-type controls. Leptin replacement converted disease resistance to susceptibility in the C57BL/6J-ob/ob mice; this was accompanied by a switch from a Th2 to Th1 pattern of cytokine release and consequent reversal of Ig subclass production. Our findings suggest that leptin is required for the induction and maintenance of an effective proinflammatory immune response in the CNS.
Plasmin-Coated Borrelia burgdorferi Degrades Soluble and Insoluble Components of the Mammalian Extracellular Matrix (1999)

Borrelia burgdorferi, the spirochetal agent of Lyme disease, binds plasminogen in vitro. Exogenously provided urokinase-type plasminogen (PLG) activator (uPA) converts surface-bound PLG to enzymatically active plasmin. In this study, we investigated the capacity of a B. burgdorferi human isolate, once complexed with plasmin, to degrade purified extracellular matrix (ECM) components and an interstitial ECM. In a modified enzyme-linked immunosorbent assay using immobilized, soluble ECM components, plasmin-coated B. burgdorferi degraded fibronectin, laminin, and vitronectin but not collagen. Incubation of plasmin-coated organisms with biosynthetically radiolabeled native ECM resulted in breakdown of insoluble glycoprotein, other noncollagenous proteins, and collagen, as measured by release of solubilized radioactivity. Radioactive release did not occur with untreated spirochetes or spirochetes treated with uPA or PLG alone. Kinetic and inhibition studies suggested that the breakdown of collagen was indirect and due to prior disruption of supportive ECM proteins. B. burgdorferi is an invasive bacterial pathogen that may benefit by use of the host's plasminogen activation system. The results of this study have identified mechanisms in which the spirochete can use this borrowed proteolytic activity to enhance invasiveness.
Colocalisation of Vascular Endothelial Growth Factor and Its Flt-1 Receptor in Human Placenta (1995)

Vascular endothelial growth factor (VEGF) is an angiogenic protein which acts on both endothelial and trophoblast cells. In first trimester placenta, VEGF immunoreactive protein was detected in cytotrophoblast shell suggesting a role in the regulation of cytotrophoblast growth and differentiation as they also expressed VEGF receptor (flt-1) protein. VEGF and flt-1 immunoreactive proteins were expressed in Hofbauer cells within the villous mesenchyme, macrophages and in maternal decidual cells while weak VEGF immunoreactive protein was seen in syncytiotrophoblast surrounding the placental villi in first and second trimester placentae. At term, there was relatively weak VEGF and flt-1 immunostaining in the syncytiotrophoblast while intense VEGF immunostaining was seen in the Hofbauer and maternal decidual cells. Extravillous trophoblast showed immunostaining for flt-1 but no staining for VEGF. Both amnion and chorion expressed strong VEGF immunoreactivity throughout gestation. Smooth muscle cells surrounding the vein and arteries of the umbilical cord showed weak VEGF immunoreactivity while no immunoreactivity was localised in endothelial cells. VEGF stimulated parathyroid hormone-related protein (PTHrP) release (mean (+/- SD): basal, 0.96 +/- 0.03; 10 ng/ml VEGF165, 2.07 +/- 0.18 and 20 ng/ml VEGF165, 2.43 +/- 0.18 pmol/l/well of PTHrP1-86) in condition medium from immortalised first trimester trophoblast cell line. These results suggest that VEGF in addition to acting as an autocrine mitogen for trophoblast proliferation may also function as a paracrine mediator of vascular tone by releasing vasorelaxants from trophoblasts.
Risk Status of Stroke among Adults and the Effectiveness of an Awareness Program on Primary Prevention of Stroke (2011)

Background:Stroke is emerging as a major public health problem. Identifying risk factor and providing education on primary prevention will help to reduce the burden of stroke in the community.
Objective :To identify the risk status of stroke among adults and to find association between the risk status of adults and selected variables such as age, gender, education, occupation and source of information.
Material and Method :Descriptive study conducted in Kaviyur village of Pathanamthitta District, Kerala. A total of 410 adults (45 years and above), were given a self administered stroke risk assessment questionnaire followed by Blood pressure, height and weight measurement.
Results: Around 52.7% were more than 55 years and 58. 8% were females. Half of the samples (51.5%) were having SSLC up to Pre University level and found that among the samples 45.4% were house wives. It was noted that majority of the participants 73.9% were getting health information from television. The major risk factors of stroke Hypertension (38%), Smoking (17.1%), High cholesterol (25.1%), and Diabetes (24.4%) and lack of exercise (53.7%) were identified among 410 samples.
Conclusion: People were often unable to identify their health condition as risk factor of stroke. Risk perception through mass education on primary prevention of stroke will help to control of modifiable risk factors.
Performance Evaluation of a Novel Type of Low-Energy Electron Microscope (1990)

During the last few years the investigation of clean and adsorbate-covered solid surfaces as well as thin-film growth and molecular dynamics have given rise to a constant demand for high-resolution imaging microscopy with reflected and diffracted low energy electrons as well as photo-electrons. A recent successful implementation of a UHV low-energy electron microscope by Bauer and Telieps encouraged us to construct such a low energy electron microscope (LEEM) for high-resolution imaging incorporating several novel design features, which is described more detailed elsewhere. The constraint of high field strength at the surface required to keep the aberrations caused by the accelerating field small and high UV photon intensity to get an improved signal-to-noise ratio for photoemission led to the design of a tetrode emission lens system capable of also focusing the UV light at the surface through an integrated Schwarzschild-type objective. Fig. 1 shows an axial section of the emission lens in the LEEM with sample (28) and part of the sample holder (29). The integrated mirror objective (50a, 50b) is used for visual in situ microscopic observation of the sample as well as for UV illumination. The electron optical components and the sample with accelerating field followed by an einzel lens form a tetrode system. In order to keep the field strength high, the sample is separated from the first element of the einzel lens by only 1.6 mm. With a numerical aperture of 0.5 for the Schwarzschild objective the orifice in the first element of the einzel lens has to be about 3.0 mm in diameter. Considering the much smaller distance to the sample one can expect intense distortions of the accelerating field in front of the sample. Because the achievable lateral resolution depends mainly on the quality of the first imaging step, careful investigation of the aberrations caused by the emission lens system had to be done in order to avoid sacrificing high lateral resolution for larger numerical aperture.
Squamous Cell Carcinoma of the Lung: Molecular Subtypes and Therapeutic Opportunities (2012)

Lung cancer is the leading cause of cancer-related deaths worldwide. Next to adenocarcinoma, squamous cell carcinoma (SCC) of the lung is the most frequent histologic subtype in non-small cell lung cancer. Encouraging new treatments (i.e., bevacizumab, EGFR tyrosine kinase inhibitors, and ALK inhibitors) have afforded benefits to patients with adenocarcinoma, but unfortunately the same is not true for SCC. However, many genomic abnormalities are present in SCC, and there is growing evidence of their biologic significance. Thus, in the short term, the molecular characterization of patients with SCC in modern profiling platforms will probably be as important as deciphering the molecular genetics of adenocarcinoma. Patients with SCC of the lung harboring specific molecular defects that are actionable (e.g., fibroblast growth factor receptor 1 amplification, discoidin domain receptor 2 mutation, and phosphoinositide 3-kinase amplification) should be enrolled in prospective clinical trials targeting such molecular defects.
Expression of transforming growth factor beta is elevated in human and experimental diabetic nephropathy. (1993)

Diabetes is now the most common cause of progressive kidney failure leading to dialysis or transplantation. The central pathological feature of diabetic nephropathy is accumulation of extracellular matrix within the glomeruli. The factors in the diabetic milieu responsible for extracellular matrix accumulation are not understood. Here we report that in glomeruli of rats made diabetic there is a slow, progressive increase in the expression of transforming growth factor beta (TGF-beta) mRNA and TGF-beta protein. A key action of TGF-beta is induction of extracellular matrix production, and specific matrix proteins known to be induced by TGF-beta were increased in diabetic rat glomeruli. These proteins include an alternatively spliced form of fibronectin, tenascin, and the proteoglycan biglycan. TGF-beta has not previously been implicated in the matrix accumulation that occurs in the diabetic kidney. Glomeruli from humans with diabetic nephropathy also showed a striking increase in immunoreactive TGF-beta protein and deposition of the special form of fibronectin, whereas glomeruli from normal subjects or from individuals with other glomerular diseases (where extracellular matrix accumulation is not a feature) were negative or barely positive. These results implicate TGF-beta in the pathogenesis of diabetic nephropathy.
COL6A1 genomic deletions in Bethlem myopathy and Ullrich muscular dystrophy (2005)

We have identified highly similar heterozygous COL6A1 genomic deletions, spanning from intron 8 to exon 13 or intron 13, in two patients with Ullrich congenital muscular dystrophy and the milder Bethlem myopathy. The 5' breakpoints of both deletions are located within a minisatellite in intron 8. The mutations cause in-frame deletions of 66 and 84 amino acids in the amino terminus of the triple-helical domain, leading to intracellular accumulation of mutant polypeptides and reduced extracellular collagen VI microfibrils. Our studies identify a deletion-prone region in COL6A1 and suggest that similar mutations can lead to congenital muscle disorders of different clinical severity.
Efficacy and safety of retaspimycin hydrochloride (IPI-504) in combination with trastuzumab in patients (pts) with pretreated, locally advanced or metastatic HER2-positive breast cancer. (2011)

590 Background: Retaspimycin hydrochloride (IPI-504) is a potent, intravenously-administered heat shock protein 90 (Hsp90) chaperone inhibitor. Hsp90 helps maintain the stability of key oncoproteins, including HER2. Preclinical studies have demonstrated the activity of IPI-504 plus trastuzumab in xenograft mouse models using trastuzumab-sensitive and trastuzumab-resistant HER2-positive cell lines. Methods: In our single-arm, phase 2 study, the overall response rate and tolerability of IPI-504 plus trastuzumab in pts with previously treated, locally advanced or metastatic HER2-positive breast cancer were evaluated. Prior treatment with trastuzumab was required and no limit of previous lines was specified. The trial used a Simon two-stage design; if the DLT rate was ≤25% and at least 2 responses were observed, the trial would be expanded. Results: 26 pts were initially treated with 300 mg/m2 IPI-504 once weekly in combination with 6 mg/kg trastuzumab once every 3 weeks. The median age was 52.5 years (range 33-72) and the median number of prior regimens received was 6 (range 2-20). Pts received a median of 3 cycles (range 1-12) of IPI-504. No DLTs were reported. The majority of AEs were grade 1 or 2, and the most common treatment-related adverse events were fatigue (46%), nausea (31%), and diarrhea (23%). Related serious adverse events were reported in 2 pts; one pt had Grade 1 diarrhea and Grade 3 hypokalemia, and the other pt had Grade 3 vomiting. Only 1 (4%) Grade 3 transaminase elevation was noted on trial, in a pt with metastatic disease to the liver. Among the 20 pts evaluable for efficacy, 1 partial response was observed (based on central, independent radiology review). Stable disease was observed in 14 pts (70%), including 1 pt (4%) with stable disease for more than 6 months. Conclusions: IPI-504 300 mg/m² IV weekly in combination with trastuzumab was well tolerated, without significant hepatic toxicity. Treatment resulted in modest clinical activity in heavily pretreated pts previously exposed to trastuzumab, but did not meet the prespecified efficacy criteria for trial expansion.