gebhart/patrepeval huggingface dataset:
Identification and Characterization of an Escherichia coli Invasion Gene Locus, ibeB , Required for Penetration of Brain Microvascular Endothelial Cells (1999)

Escherichia coli K1 is the most common gram-negative organism causing neonatal meningitis, but the mechanism by which E. coli K1 crosses the blood-brain barrier is incompletely understood. We have previously described the cloning and molecular characterization of a determinant, ibeA (also called ibe10), from the chromosome of an invasive cerebrospinal fluid isolate of E. coli K1 strain RS218 (O18:K1:H7). Here we report the identification of another chromosomal locus, ibeB, which allows RS218 to invade brain microvascular endothelial cells (BMEC). The noninvasive TnphoA mutant 7A-33 exhibited <1% the invasive ability of the parent strain in vitro in BMEC and was significantly less invasive in the central nervous system in the newborn rat model of hematogenous E. coli meningitis than the parent strain. The TnphoA insert with flanking sequences was cloned and sequenced. A 1,383-nucleotide open reading frame (ORF) encoding a 50-kDa protein was identified and termed ibeB. This ORF was found to be 97% identical to a gene encoding a 50-kDa hypothetical protein (p77211) and located in the 13-min region of the E. coli K-12 genome. However, no homology was observed between ibeB and other known invasion genes when DNA and protein databases in GenBank were searched. Like the TnphoA insertion mutant 7A-33, an isogenic ibeB deletion mutant (IB7D5) was unable to invade BMEC. A 7. 0-kb locus containing ibeB was isolated from a LambdaGEM-12 genomic library of E. coli RS218 and subcloned into a pBluescript KS vector (pKS7-7B). pKS7-7B was capable of completely restoring the BMEC invasion of the noninvasive TnphoA mutant 7A-33 and the ibeB deletion mutant IB7D5 to the level of the parent strain. More importantly, the ibeB deletion mutant IB7D5 was fully complemented by pFN476 carrying the ibeB ORF (pFN7C), indicating that ibeB is required for E. coli K1 invasion of BMEC. Taken together, these findings indicate that several E. coli determinants, including ibeA and ibeB, contribute to crossing of the blood-brain barrier.
Membrane Protein Microarrays (2002)

This paper describes the fabrication of microarrays consisting of G protein-coupled receptors (GPCRs) on surfaces coated with gamma-aminopropylsilane (GAPS). Microspots of model membranes on GAPS-coated surfaces were observed to have several desired properties-high mechanical stability, long range lateral fluidity, and a thickness corresponding to a lipid bilayer in the bulk of the microspot. GPCR arrays were obtained by printing membrane preparations containing GPCRs using a quill-pin printer. To demonstrate specific binding of ligands, arrays presenting neurotensin (NTR1), adrenergic (beta1), and dopamine (D1) receptors were treated with fluorescently labeled neurotensin (BT-NT). Fluorescence images revealed binding only to microspots corresponding to the neurotensin receptor; this specificity was further demonstrated by the inhibition of binding in the presence of excess unlabeled neurotensin. The ability of GPCR arrays to enable selectivity studies between the different subtypes of a receptor was examined by printing arrays consisting of three subtypes of the adrenergic receptor: beta1, beta2, and alpha2A. When treated with fluorescently labeled CGP 12177, a cognate antagonist analogue specific to beta-adrenergic receptors, binding was only observed to microspots of the beta1 and beta2 receptors. Furthermore, binding of labeled CGP 12177 was inhibited when the arrays were incubated with solutions also containing ICI 118551, and in a manner consistent with the higher affinity of ICI 118551 for the beta2 receptor relative to that for the beta1 receptor. The ability to estimate binding affinities of compounds using GPCR arrays was examined using a competitive binding assay with BT-NT and unlabeled neurotensin on NTR1 arrays. The estimated IC(50) value (2 nM) for neurotensin is in agreement with the literature; this agreement suggests that the receptor -G protein complex is preserved in the microspot. This first ever demonstration of direct pin-printing of membrane proteins and ligand-binding assays thereof fills a significant void in protein microchip technology--the lack of practical microarray-based methods for membrane proteins.
Transport of the antibacterial agent oxazolidin-2-one and derivatives across intestinal (Caco-2) and renal (MDCK) epithelial cell lines (1996)

The transepithelial passage of the orally bioavailable antibacterial agent oxazolidin-2-one (OXa) and 10 derivatives has been studied with human intestinal (Caco-2) and canine renal (MDCK) cell lines grown on polycarbonate filters. The transepithelial passage was assayed in the apical-to-basolateral (AP-to-BL) direction and in the opposite direction (BL to AP) in both cell lines. The observed passage rates of OXa were similar in both directions in the two cell lines, suggesting passive diffusion. This was further confirmed by the fact that transport kinetics were linear as a function of initial concentration. The rates of AP-to-BL passage of OXa and seven of the derivatives in both cell lines were linearly related to lipophilicity, whether expressed as high-passage liquid chromatography retention time or as the logarithm of the n-octanol-water partition coefficient (log P). These data suggest that the lipophilicity of OXa is important for its observed bioavailability after oral administration. Interestingly, three of the derivatives exhibited a higher passage rate than predicted by lipophilicity. Further studies indicated that this transport was saturable, similar in the two directions, and not affected by energy depletion, suggesting the presence of an additional carrier-mediated facilitated-transport mechanism.
BRAF Is a Therapeutic Target in Aggressive Thyroid Carcinoma (2006)

BRAF provides signals crucial for proliferation of thyroid carcinoma cells spontaneously harboring the (V600E)BRAF mutation and, therefore, BRAF suppression might have therapeutic potential in (V600E)BRAF-positive thyroid cancer.
AN OVERVIEW OF THE IMPACT x86 BINARY REOPTIMIZATION FRAMEWORK (1998)

this report is organized as follows: Chapter 2 provides an overview of the x86 binary reoptimization system. Chapter 3 describes our use of IMPACT&amp;apos;s low-level intermediate representation. Chapter 4 describes each of the software modules in more detail. Chapter 5 provides a summary and concluding remarks.
Making the diagnosis of Sj&ouml;gren&rsquo;s syndrome in patients with dry eye (2015)

Sjögren's syndrome (SS) is a chronic and progressive systemic autoimmune disease that often presents initially with symptoms of dry eye and dry mouth. Symptoms are often nonspecific and develop gradually, making diagnosis difficult. Patients with dry eye complaints warrant a step-wise evaluation for possible SS. Initial evaluation requires establishment of a dry eye diagnosis using a combination of patient questionnaires and objective ocular tests, including inflammatory biomarker testing. Additional work-up using the Schirmer test and tear film break-up time can differentiate between aqueous-deficient dry eye (ADDE) and evaporative dry eye. The presence of ADDE should trigger further work-up to differentiate between SS-ADDE and non-SS-ADDE. There are numerous non-ocular manifestations of SS, and monitoring for SS-related comorbid findings can aid in diagnosis, ideally in collaboration with a rheumatologist. The clinical work-up of SS can involve a variety of tests, including tear function tests, serological tests for autoantibody biomarkers, minor salivary gland and lacrimal gland biopsies. Examination of classic SS biomarkers (SS-A/Ro, SS-B/La, antinuclear antibody, and rheumatoid factor) is a convenient and non-invasive way of evaluating patients for the presence of SS, even years prior to confirmed diagnosis, although not all SS patients will test positive, particularly those with early disease. Recently, newer biomarkers have been identified, including autoantibodies to salivary gland protein-1, parotid secretory protein, and carbonic anhydrase VI, and may allow for earlier diagnosis of SS. A diagnostic test kit is commercially available (Sjö(®)), incorporating these new biomarkers along with the classic autoantibodies. This advanced test has been shown to identify SS patients who previously tested negative against traditional biomarkers only. All patients with clinically significant ADDE should be considered for serological assessment for SS, given the availability of new serological diagnostic tests and the potentially serious consequences of missing the diagnosis.
Benzothiadiazides inhibit rapid glutamate receptor desensitization and enhance glutamatergic synaptic currents (1993)

A distinctive characteristic of the AMPA subset of glutamate receptor channels is their remarkably rapid desensitization. A family of compounds, the benzothiadiazides, is described here that potently inhibit rapid glutamate receptor desensitization. The structure-activity relationships of these compounds are examined and the actions of cyclothiazide (CYZ), the most potent of these compounds, are described in detail. At the macroscopic level CYZ reduced rapid desensitization, enhancing the steady-state and peak current produced by 1 mM quisqualate with EC50 values of 14 and 12 microM, respectively, and shifted the quisqualate peak current concentration-response relation to the left. The slight outward rectification of the steady-state quisqualate current-voltage relationship was reduced by CYZ. At the microscopic level CYZ caused glutamate to induce long bursts of channel openings, and greatly increased the number of repeated openings. At 10 microM CYZ did not have measurable effects on the fast component of deactivation nor did it have statistically significant effects on the distribution of the faster components of glutamate-induced burst duration. In contrast, 10 microM CYZ increased the amplitude and significantly prolonged the duration of the spontaneous miniature EPSCs. The identification and characterization of this new family of gating modifiers may further facilitate the investigation into the mechanisms underlying rapid glutamate receptor desensitization and the physiological roles that it may serve.
Pathotropic nanoparticles for cancer gene therapy Rexin-G™ IV: Three-year clinical experience (2006)

Metastatic cancer is a life-threatening illness with a predictably fatal outcome, thereby representing a major unmet medical need. In 2003, Rexin-G became the world's first targeted injectable vector approved for clinical trials in the treatment of intractable metastatic disease. Uniquely suited, by design, to function within the context of the human circulatory system, Rexin-G is a pathotropic (disease-seeking) gene delivery system bearing a designer killer gene; in essence, a targeted nanoparticle that seeks out and selectively accumulates in metastatic sites upon intravenous infusion. The targeted delivery of the cytocidal gene to primary tumors and metastatic foci, in effective local concentrations, compels both cancer cells and tumor-associated neovasculature to self-destruct, without causing untoward collateral damage to non-target organs. In this study: i) we report the results of three distinctive clinical studies which demonstrate the initial proofs of concept, safety, and efficacy of Rexin-G when used as a single agent for advanced or metastatic cancer, ii) we introduce the quantitative foundations of an innovative personalized treatment regimen, designated the 'Calculus of Parity', based on a patient's calculated tumor burden, iii) we propose a refinement of surrogate end-points commonly used for defining success in cancer therapy, and iv) we map out a strategic plan for the accelerated approval of Rexin-G based on the oncologic Threshold of Credibility paradigm being developed by the Food and Drug Administration.
Recent advances in the management of systemic lupus erythematosus (2018)

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease presenting highly heterogeneous clinical manifestations and multi-systemic involvement. Patients are susceptible to relapse- and remission, thus making management challenging. Moreover, a considerable number of side effects may occur with conventional therapies; therefore, there is clearly a need for new therapeutic strategies. Since the pathogenesis of SLE is highly complex, it is far from being fully understood. However, greater understanding of the pathways and of the cellular and molecular mediators involved in SLE is being achieved. Emerging evidence has allowed the development of new biological therapeutic options targeting crucial molecular mediators involved in the pathogenesis of SLE. This literature review analyzes the availability of biological and target-directed treatments, phase II and III trials, and new therapies that are being developed for the treatment of SLE.
Kinetics of the Competitive Degradation of Deoxyribose and Other Molecules by Hydroxyl Radicals Produced by the Fenton Reaction in the Presence of Ascorbic Acid (1995)

The competition method in which the Fenton reaction is employed as an .OH radical generator and deoxyribose as a detecting molecule, has been used to determine the rate constants for reactions of the .OH radical with its scavengers. Nonlinear competition plots were obtained for those scavengers which reacted with the Fenton reagents (Fe2+ or H2O2). Ascorbic acid is believed to overcome this problem. We have investigated the kinetics of deoxyribose degradation by .OH radicals generated by the Fenton reaction in the presence of ascorbic acid, and observed that the inclusion of ascorbic acid in the Fenton system greatly increased the rate of .OH radical generation. As a result, the interaction between some scavengers and the Fenton reagents became negligeable and linear competition plots of A degree/A vs scavenger concentrations were obtained. The effects of experimental conditions such as, the concentrations of ascorbic acid, deoxyribose, H2O2 and Fe(2+)-EDTA, the EDTA/Fe2+ ratio as well as the incubation time, on the deoxyribose degradation and the determination of the rate constant for mercaptoethanol chosen as a reference compound were studied. The small standard error, (6.76 +/- 0.21) x 10(9) M-1s-1, observed for the rate constant values for mercaptoethanol determined under 13 different experimental conditions, indicates the latter did not influence the rate constant determination. This is in fact assured by introducing a term, kx, into the kinetic equation. This term represents the rate of .OH reactions with other reagents such as ascorbic acid, Fe(2+)-EDTA, H2O2 etc. The agreement of the rate constants obtained in this work with that determined by pulse radiolysis techniques for cysteine, thiourea and many other scavengers, suggests that this simple competition method is applicable to a wide range of compounds, including those which react with the Fenton reagents and those whose solubility in water is low.
Thickness and stacking geometry effects on high frequency overtone and combination Raman modes of graphene (2012)

We investigate two high frequency Raman overtone and combination modes of graphene named 2D' and 2D + G bands, and located at ~3240 and ~ 4260 cm –1 , respectively. The graphene thickness and stacking geometry effects for these two modes are systematically studied. The features of the 2D' band, which arises from intravalley double resonance, are not sensitive to the variation of thickness with single Lorentzian peak and fixed linewidth. We explain it theoretically by calculating the phonon dispersion mode in k ‐space and find that the flat band region of longitudinal optical phonon near Γ point is the mechanism leading to the 2D' band nonsplit. With the thickness increasing, the band position exhibits blueshift and the linewidth increases for the 2D + G band. With changing thickness and stacking geometry of graphene, the intensities of these two high‐frequency bands show obvious different evolution compared with that of G band. Copyright © 2012 John Wiley &amp; Sons, Ltd.
[Biological characteristics of residual leukemic cells and their drug-resistant regrowth]. (1997)

Bone marrow stromal layer was the vital microenvironment for the residual leukemic cells to survive and regrow, and might increase the drug-resistance by up-regulating bcl-2 gene expression.
A low-voltage triggering SCR for on-chip ESD protection at output and input pads (1990)

A novel silicon-controlled rectifier (SCR) structure for on-chip protection against electrostatic discharge (ESD) stress at output or input pads is presented. The SCR switches to an ON state at a trigger voltage determined by the gate length of an incorporated nMOS-like structure. Thus the SCR can be designed to consistently trigger at a voltage low enough to protect nMOS transistors from ESD. The capability of protection circuits using the new SCR design is experimentally demonstrated. The tunability of the SCR trigger voltage with reference to the nMOS breakdown voltage is successfully exploited to improve the human-body-model ESD failure threshold of an output buffer from 1500 V to 5000 V
Evidence for transcriptional regulation of orotidine-5'-phosphate decarboxylase in yeast by hybridization of mRNA to the yeast structural gene cloned in Escherichia coli. (1979)

From a large population of strains of Escherichia coli carrying shear fragments of yeast (Saccharomyces cerevisiae) DNA attached by in vitro recombination to the plasmid vector pMB9, two hybrid plasmids were selected that relieve the pyrimidine requirement of nonreverting pyrF mutants of E. coli. An 1100-base-pair DNA fragment common to the two complementing plasmids was recloned into another plasmid vector, pBR322; these new hybrids retained the ability to specify orotidine-5'-phosphate decarboxylase (orotidine-5'-phosphate carboxy-lyase, EC 4.1.1.23) synthesis in E. coli. Evidence is presented that this common fragment is yeast DNA and thus apparently carried the structural information for yeast orotidine-5'-phosphate decarboxylase, the product of yeast gene ura3. A hybrid plasmid containing the 1100-base-pair fragment was used to measure levels of putative ura3 mRNA from yeast cultures labeled with [3H]adenine, ura3 mRNA was unstable with an apparent half-life of 10.5 min. Under different circumstances previously shown to alter the level of orotidine-5'-phosphate decarboxylase in yeast, a coordinate variation in proportion of labeled RNA complementary to the hybrid plasmid was found. These data support the hypothesis that regulation of the ura3 gene in yeast is at the level of transcription.
Three-dimensional model of cardiac electromechanics: cell to organ (2002)

We describe a new computational model that integrates the cellular biophysics of ventricular myocytes into structurally detailed three-dimensional models of the ventricular walls during the whole cardiac cycle. The new model is suitable for investigating hypotheses regarding excitation-contraction coupling in the intact heart.
Anti-CD137 mAb Deletes Both Donor CD4+and CD8+T Cells in Acute Graft-versus-host Disease (2011)

We previously demonstrated that in vivo engagement of CD137, a member of TNF receptor superfamily, can delete allorective CD4(+) T cells through the induction of activation-induced cell death (AICD) in chronic graft-versus-host disease (cGVHD) and subsequently reverse established cGVHD. In this study, we further showed that agonistic anti-CD137 mAb was highly effective in triggering AICD of donor CD8(+) T cells as well as donor CD4(+) T cells in the C57BL/6→unirradiated (C57BL/6 × DBA/2)F1 acute GVHD model. Our results suggest that strong allostimulation should facilitate AICD of both alloreactive CD4(+) and CD8(+) T cells induced by CD137 stimulation. Therefore, depletion of pathogenic T cells using agonistic anti-CD137 mAb combined with potent TCR stimulation may be used to block autoimmune or inflammatory diseases mediated by T cells.
A Novel Type of Vascular Endothelial Growth Factor, VEGF-E (NZ-7 VEGF), Preferentially Utilizes KDR/Flk-1 Receptor and Carries a Potent Mitotic Activity without Heparin-binding Domain (1998)

Vascular endothelial growth factor (VEGF) mediates endothelial cell proliferation, angiogenesis, and vascular permeability via the endothelial cell receptors, KDR/Flk-1 and Flt-1. Recently, a gene encoding a polypeptide with about 25% amino acid identity to mammalian VEGF was identified in the genome of Orf virus (OV), a parapoxvirus that affects sheep and goats and occasionally, humans, to generate lesions with angiogenesis. In this study, we examined the biological activities and receptor of OV-derived NZ-7 VEGF (VEGF-E). VEGF-E was found to be a dimer of about 20 kDa with no basic domain nor affinity for heparin column, similar to VEGF121 subtype. VEGF121 has 10-100-fold less endothelial cell mitotic activity than VEGF165 due to lack of a heparin-binding basic region. Interestingly, however, VEGF-E showed almost equal levels of mitotic activity on primary endothelial cells and vascular permeability activity as VEGF165. Furthermore, VEGF-E bound KDR/Flk-1 (VEGFR-2) and induced its autophosphorylation to almost the same extent as VEGF165, but did not bind Flt-1 (VEGFR-1) nor induce autophosphorylation of Flt-1. These results indicate that VEGF-E is a novel type of endothelial growth factor, utilizing only one of the VEGF receptors, and carrying a potent mitogenic activity without affinity to heparin.
A prospective microbiologic surveillance program to detect and prevent the transfusion of bacterially contaminated platelets (1993)

After two patients received bacterially contaminated platelet transfusions, a prospective surveillance program was instituted to perform Gram staining and microbiologic culturing of platelets at the time of transfusion. In 12 months, 3141 random-donor platelet pools (prepared from 14,481 units) and 2476 single-donor apheresis units were cultured. All single-donor apheresis units were sterile, but 6 (0.19%) of the random-donor pools were found to be bacterially contaminated, with 1 unit of 5 in the pool being the source in each case. Contaminants were Staphylococcus epidermidis (4 cases), Bacillus cereus (1), and Staphylococcus aureus (1) at counts of 0.5 x 10(2) to 10(11) colony-forming units per mL in platelet pools and 10(3) to 10(13) colony-forming units per mL in source units. The contamination rate for units transfused at < or = 4 days (1.8/10,000) was significantly lower than that at 5 days (11.9/10,000; p < 0.05), as was the magnitude of contamination (p < 0.05). Use of the pretransfusion Gram stain on 4- and 5-day-old platelet pools was 100 percent sensitive (4/4 true positives) and 99.93 percent specific (1 false positive) in detecting contaminated pools. These data define the extent and magnitude of platelet bacterial contamination and demonstrate the efficacy of the pretransfusion Gram stain on platelet units stored for 4 and 5 days in preventing the transfusion of heavily contaminated units. It is concluded that the risk of platelet contamination is related to the duration of component storage.(ABSTRACT TRUNCATED AT 250 WORDS)