gebhart/patrepeval huggingface dataset:
Proteinase-Activated Receptor-2 Mediates Itch: A Novel Pathway for Pruritus in Human Skin (2003)

We examined whether neuronal proteinase-activated receptor-2 (PAR-2) may be involved in pruritus of human skin. The endogenous PAR-2 agonist tryptase was increased up to fourfold in atopic dermatitis (AD) patients. PAR-2 was markedly enhanced on primary afferent nerve fibers in skin biopsies of AD patients. Intracutaneous injection of endogenous PAR-2 agonists provoked enhanced and prolonged itch when applied intralesionally. Moreover, itch upon mast cell degranulation was abolished by local antihistamines in controls but prevailed in AD patients. Thus, we identified enhanced PAR-2 signaling as a new link between inflammatory and sensory phenomena in AD patients. PAR-2 therefore represents a promising therapeutic target for the treatment of cutaneous neurogenic inflammation and pruritus.
Electrothermal frequency tuning of folded and coupled vibrating micromechanical resonators (1998)

The use of constrained thermal expansion to tune the resonant frequency of vibrating micromechanical resonators is explored. A simple model is developed to predict the power sensitivity obtained with folded and unfolded geometries, including the effects of electrothermal heating, and conduction and convection cooling. It is shown that the sensitivity of folded structures can change sign as the ambient gas pressure is lowered in contrast to the behavior of unfolded structures. Tuning is then by tensile axial stress rather than compressive stress. Using folded laterally resonant bulk-micromachined comb-drive electrostatic actuators, tuning ranges of -25% and +50% are obtained (at atmospheric pressure and at 10 mTorr, respectively, with powers of 10 and 1.5 mW, respectively). A nested coupled resonator is then presented in which the frequency of one resonator may be tuned without effecting that of the other, thus allowing frequency matching to be obtained.
Breast cancer extracellular matrix gene cluster: Association with prognosis and response to tamoxifen. (2007)

A6 Background: We previously identified an extracellular matrix (ECM) gene cluster from which the expression was associated with response to first-line tamoxifen therapy in metastatic breast cancer patients (Jansen et al J Clin Oncol 2006). This ECM gene cluster comprises six genes, collagen 1A1 (COL1A1), fibronectin (FN1), lysyl oxidase (LOX), secreted protein acidic cysteine-rich (SPARC), tissue inhibitor of metalloproteinase 3 (TIMP3) and tenascin C (TNC). In this study we determined the association of these ECM genes with response to tamoxifen monotherapy, metastatic potential, or both.  Methods: We have measured the ECM geneexpression levels by real-time polymerase chain reaction in 1,286 primary breast tumor specimens. Expression levels were normalized to housekeeper gene levels and were analyzed as continuous variables in relation to clinicopathologic factors for all patients. In addition, in a multivariate analysis the expression levels were compared to traditional prognostic and predictive factors (age, menopausal status, tumor size, grade, LN status, ER, PgR, dominant site of relapse and disease-free interval).  Results: TIMP3, FN1, LOX and SPARC expression was significantly associated with distant metastasis-free survival (MFS) in 680 lymph node negative untreated patients (p
The effect of crystallization conditions on radiationinduced crosslink formation in polyethylene (1965)

Abstract Annealing treatment before irradiation was observed to change the radiation-induced gelation behaviour of single crystals. After a decrease on short annealing times the gel content increases on prolonged annealing and approaches the behaviour of the bulk. Variations in lamellar contact are invoked to account for this behaviour. In other experiments single crystal samples were irradiated first and annealed subsequently. It was found that even a high degree of crosslinking which might be expected to immobilize the chains did not prevent re-folding. The conclusion is reached that the folds are preferential sites where the crosslinks form, the ineffective ones giving rise to small rings which can thread through the lattice on re-folding. Lattice distortions are expected to occur during this process and are in fact indicated by the x-ray diffraction pattern.
Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting (1996)

Malaria infection induces the production of serum antibodies to a variety of malaria antigens but the prevalence of antibodies to any particular antigen is typically much less than 100%. It has been assumed that non-responsiveness to defined antigens in malaria immune subjects is due to HLS-mediated restriction of the immune response. In this study we have investigated the role of HLA and non-HLA genes in the antibody response to two merozoite surface antigens (MSP1 and MSP2) and a sexual stage antigen (Ps260/230) of Plasmodium falciparum, and conclude that host genotype is not a major determinant of responsiveness. Although antibody levels vary in accordance with seasonal variations in malaria transmission in semi-immune children, antibody levels remain stable in clinically immune adults. Antigen recognition is selective with individual donors showing consistent high titre responses to some antigens/epitopes whilst consistently failing to recognize adjacent regions/epitopes of the same protein. An alternative explanation, consistent with the data presented here, is that selective antibody responses to malaria antigens in immune individuals result from a process akin to clonal imprinting (original antigenic sin).
Ion-Pairing Molecular Recognition in Water:  Aggregation at Low Concentrations That Is Entropy-Driven (2002)

Investigations into the thermodynamic parameters that characterize the binding of citrate to tris-guanidinium host 1 in water are reported. The parameters K(a), DeltaH degrees, DeltaS degrees, and DeltaG degrees for the binding event were quantified using isothermal titration calorimetry (ITC) techniques. The 1:1 binding stoichiometry was verified by a Job plot derived from NMR data, and the microcalorimetry data was collected for solutions of 1 and citrate ranging from 1 to 100 mM using phosphate buffer concentrations of 5 and 103 mM. At low buffer concentrations (low ionic strength) complexes with greater than 1:1 stoichiometries were observed by ITC, and K(1) was determined to range from 2.0 x 10(3) to 3.0 x 10(3) M(-1). At higher buffer concentrations (high ionic strength) the higher-order complexes were not detected, and K(1) was determined to be 409 M(-1). The 1:1 association of host 1 and citrate is characterized by a large favorable entropy component and negative enthalpy. However, the complexes with higher-order stoichiometry arise from desolvation processes that result from the association of polyions in aqueous media and is entirely entropy driven. This leads to an unusual observation: the dilution of one component of the host/guest complex leads to the formation of the higher-order complexes. The reason for this observation is discussed.
A mutation in reverse transcriptase of bis(heteroaryl)piperazine-resistant human immunodeficiency virus type 1 that confers increased sensitivity to other nonnucleoside inhibitors. (1993)

Several nonnucleoside inhibitors of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) have been described, including Nevirapine, thiobenzimidazolone (TIBO) derivatives, pyridinone derivatives such as L-697,661, and the bis(heteroaryl)piperazines (BHAPs). HIV-1 resistant to L-697,661 or Nevirapine emerges rapidly in infected patients treated with these drugs, and the resistance is caused primarily by substitutions at amino acids 181 and 103 of RT that also confer cross resistance to the other nonnucleoside inhibitors. We describe derivation and characterization of two BHAP-resistant HIV-1 variants that differ from this pattern of cross resistance. With both variants, HIV-1 resistance to BHAP RT inhibitors was caused by a RT mutation that results in a proline-to-leucine substitution at amino acid 236 (P236L). Rather than conferring cross resistance to other RT inhibitors, this substitution sensitized RT 7- to 10-fold to Nevirapine, TIBO R82913, and L-697,661 without influencing sensitivity to nucleoside analogue RT inhibitors. This sensitization caused by P236L was also observed in cell culture with BHAP-resistant HIV-1. The effects of the P236L RT substitution suggest that emergence of BHAP-resistant virus in vivo could produce a viral population sensitized to inhibition by these other nonnucleoside RT inhibitors.
High resolution Fourier transform spectroscopy of jet-cooled molecules (2000)

The spectroscopic literature reporting on the coupling between Fourier transform spectrometers and supersonic jet expansions is reviewed. Particular attention is devoted to high resolution infrared absorption experiments. Short and much longer introductions are provided on Fourier transform spectrometers and jets, respectively, with emphasis on the problems raised by coupling the two techniques. Details of the optical designs reported in the literature are considered. The literature on all the molecules studied is tabulated. Some of the spectroscopic results are highlighted, in particular those obtained at Universite Libre de Bruxelles.
Strategies to prolong the plasma residence time of peptidedrugs (2010)

Well established as well as recently developed strategies to prevent the fast clearance of peptide drugs from the circulation are reviewed.
Immunotherapy of Cancer with 4-1BB (2012)

4-1BB (CD137), a member of the TNF receptor superfamily, is an activation-induced T-cell costimulatory molecule. Signaling via 4-1BB upregulates survival genes, enhances cell division, induces cytokine production, and prevents activation-induced cell death in T cells. The importance of the 4-1BB pathway has been underscored in a number of diseases, including cancer. Growing evidence indicates that anti-4-1BB monoclonal antibodies possess strong antitumor properties, which in turn are the result of their powerful CD8+ T-cell activating, IFN-γ producing, and cytolytic marker-inducing capabilities. In addition, combination therapy of anti-4-1BB with other anticancer agents, such as radiation, has robust tumor-regressing abilities against nonimmunogenic or poorly immunogenic tumors. Furthermore, the adoptive transfer of ex vivo anti-4-1BB-activated CD8+ T cells from previously tumor-treated animals efficiently inhibits progression of tumors in recipient mice that have been inoculated with fresh tumors. In addition, targeting of tumors with variants of 4-1BBL directed against 4-1BB also have potent antitumor effects. Currently, a humanized anti-4-1BB is in clinical trials in patients with solid tumors, including melanoma, renal carcinoma, and ovarian cancer, and so far seems to have a favorable toxicity profile. In this review, we discuss the basis of the therapeutic potential of targeting the 4-1BB-4-1BBL pathway in cancer treatment.
Photodynamic Efficiency of Diethylene Glycol-Linked Glycoconjugated Porphyrins in Human Retinoblastoma Cells (2006)

Photodynamic therapy (PDT) is emerging as a new strategy for the conservative treatment of hereditary retinoblastoma. The glycoconjugated porphyrins TPP(p-Deg-O-alpha-GalOH)(3), TPP(p-Deg-O-beta-GalOH)(3), TPP(p-Deg-O-alpha-ManOH)(3), and their S-analogues were synthesized to obtain efficient photosensitizers with some retinoblastoma cell affinity. In these systems, a sugar motif and porphyrin core were linked by a diethylene glycol spacer (Deg). Cellular uptake, localization, and photoactivity have been examined in human retinoblastoma cells (Y79). After preincubation with corresponding glycosylated albumin, the uptake of TPP(p-Deg-O-beta-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) was 40-45% inhibited, indicating a possible cell-sugar-receptor saturation. High photoactivity was observed for the two alpha-galacto/manno porphyrins 8 and 10 (LD(50) = 0.05 and 0.35 muM, respectively) at 514 nm and low fluence (1 J/cm(2)). Analysis by MALDI-TOF mass spectrometry only indicated a small metabolic cleavage of the O-glycoconjugates and a good stability of the S-glycoside porphyrins. On the basis of these in vitro data, TPP(p-Deg-O-alpha-GalOH)(3) and TPP(p-Deg-O-alpha-ManOH)(3) were selected for in vivo studies.
Dissociation and reassembly of Escherichia coli type 1 pili (1981)

Escherichia coli type 1 pili, which mediate the mannose-sensitive adherence of the bacterium to eucaryotic cells, are comprised of very stable arrays of pilin protein subunits (molecular weight, approximately 17,000). Previous methods for the dissociation of pili caused their irreversible denaturation. We have found that incubation of pili in saturated guanidine hydrochloride at 37 degrees C led to their complete dissociation, as evidenced by nephelometry and electron microscopy. Gel chromatography of the dissociated pili on a Sepharose CL-6B column in the presence of saturated guanidine hydrochloride yielded a single protein peak with a molecular weight corresponding to that of pilin. Dialysis of this peak against 5 mM tris(hydroxymethyl)aminomethane hydrochloride (pH 8.0) and rechromatography in the same buffer afforded a major protein peak, probably consisting of pilin dimers. About 25% of the protein in this peak bound to a mannan-sepharose column and could be eluted with methyl alpha-D-mannoside. The pilin dimer gave a single protein band upon polyacrylamide gel electrophoresis in the presence of 0.1% sodium dodecyl sulfate (molecular weight, 16,600) or 10 M urea and penetrated completely into 7% gels in the absence of denaturants. Reassembly of the pilin dimers into pili was achieved upon dialysis against the tris(hydroxymethyl)aminomethane buffer containing 5 mM MgCl2, as observed by electron microscopy. Thus, the conditions used allow renaturation of the dissociated subunits and may aid in further studies of the structure-function relationship of pili.
Human respiratory syncytial virus glycoprotein G expressed from a recombinant vaccinia virus vector protects mice against live-virus challenge (1986)

Recombinant vaccinia virus vectors were constructed which expressed the major surface glycoprotein G of human respiratory syncytial (RS) virus. The biological activity of the G protein expressed from these vectors was assayed. Inoculation of rabbits with live recombinant virus induced high titers of antibody which specifically immunoprecipitated RS virus G protein and was capable of neutralizing RS virus infectivity. Immunization of mice by either the intranasal or the intraperitoneal route with recombinant virus that expressed only the G protein resulted in complete protection of the lower respiratory tract upon subsequent challenge with live RS virus.
Chromosomal Imbalance in the Aniridia-Wilms' Tumor Association: 11p Interstitial Deletion (1978)

The triad of aniridia, ambiguous genitalia, and mental retardation (AGR triad) is the characteristic clinical feature of three unrelated patients with previously unreported chromosome 11 short arm interstitial deletions. A Wilms' tumor in one patient establishes one cause for the aniridia-Wilms' tumor association. The genetic heterogeneity of aniridia, the AGR triad, and Wilms' tumor are demonstrated, and Wilms' tumor is indicated to be a neoplastic birth defect which can result from a variety of embryologic insults, some of which may be chromosomal or heritable.
High-Dose Chemotherapy with Hematopoietic Stem-Cell Rescue for Multiple Myeloma (2003)

High-dose therapy with autologous stem-cell rescue is an effective first-line treatment for patients with multiple myeloma who are younger than 65 years of age.
Stability Improvement of Electrospun Chitosan Nanofibrous Membranes in Neutral or Weak Basic Aqueous Solutions (2006)

Further utilization of chitosan nanofibrous membranes that are electrospun from chitosan solutions in trifluoroacetic acid (TFA) with or without dichloromethane (DCM) as the modifying cosolvent is limited by the loss of the fibrous structure as soon as the membranes are in contact with neutral or weak basic aqueous solutions due to complete dissolution of the membranes. Dissolution occurs as a result of the high solubility in these aqueous media of -NH(3)(+)CF(3)COO(-) salt residues that are formed when chitosan is dissolved in TFA. Traditional neutralization with a NaOH aqueous solution only maintained partial fibrous structure. Much improvement in the neutralization method was achieved with the saturated Na(2)CO(3) aqueous solution with an excess amount of Na(2)CO(3)(s) in the solution. We showed that electrospun chitosan nanofibrous membranes, after neutralization in the Na(2)CO(3) aqueous solution, could maintain its fibrous structure even after continuous submersion in phosphate buffer saline (pH = 7.4) or distilled water for 12 weeks.
Seeded Semicontinuous Emulsion Copolymerization of Butyl Acrylate with Cross-Linkers (2005)

The seeded semicontinuous emulsion copolymerization of butyl acrylate (BA) with divinyl monomers (butanediol diacrylate, BDA, and allyl methacrylate, AMA), at 80 °C and using potassium persulfate as initiator was investigated. Particularly, the study of the influence of the type and amount of cross-linkers on the kinetics, level of branching, cross-linking density, gel fraction, sol molecular weight, and latex film mechanical properties (i.e., glass transition temperature, Tg, storage modulus, and molecular weight between entanglements, Me) produced during the polymerizations was considered. The results showed that the most reactive cross-linker, BDA, produced the less cross-linked, branched, and gel-containing polymer. Mechanical property data confirmed this unexpected trend as the copolymer made with BDA exhibited the weakest mechanical properties. These results were explained by the higher occurrence of primary cyclization reactions in the case of BDA.
Protein-protein interactions : methods and applications (2004)

Proteins continuously interact with each other to determine cell fate. Consequently, an examination of just when such protein-protein interactions occur and how they are controlled is essential for understanding the molecular mechanism of biological processes, elucidating the molecular basis of diseases, and identifying potential targets for therapeutic interventions. In Protein-Protein Interactions: Methods and Applications, leading experts describe in detail their highly successful biochemical, biophysical, genetic, and computational techniques for studying these interactions. Their readily reproducible methods demonstrate how to identify protein interaction partners, qualitatively or quantitatively measure protein-protein interactions, monitor protein-protein interactions as they occur in living cells, and determine interaction interfaces. The techniques described utilize a variety of cutting-edge technologies, including surface plasmon resonance (SRP), fluorescence resonance energy transfer (FRET), fluorescence polarization (FP), isothermal titration calorimetry (ITC), circular dichroism (CD), protein fragment complementation assays (PCA), various two-hybrid systems, and proteomics- and bioinformatics-based approaches, such as the Scansite program for computational analysis. Each time-tested protocol includes a background introduction outlining the principle behind the technique, lists of equipment and reagents, and tips on troubleshooting and avoiding known pitfalls. Authoritative and highly practical, Protein-Protein Interactions: Methods and Applications offers both beginning and experienced investigators a full range of the powerful tools needed for deciphering how proteins interact to form biological networks, as well as for unraveling protein-protein interactions in disease in the search for novel therapeutic targets
Cetuximab: its unique place in head and neck cancer treatment (2013)

Head and neck cancer is the sixth most common cancer worldwide. At present, globally about 650,000 new cases of squamous cell carcinoma of the head and neck (SCCHN) are diagnosed each year. The epidermal growth factor receptor (EGFR) is almost invariably expressed in SCCHN. Overexpression of the EGFR is a strong and independent unfavorable prognostic factor in SCCHN. Cetuximab is a chimeric monoclonal antibody, which binds with high affinity to the extracellular domain of the human EGFR, blocking ligand binding, resulting in inhibition of the receptor function. It also targets cytotoxic immune effector cells towards EGFR-expressing tumor cells (antibody dependent cell-mediated cytotoxicity). The addition of cetuximab to radiotherapy (RT) improves locoregional control and survival when compared to RT alone. The addition of cetuximab to platinum-based chemoradiation (CRT) is feasible but does not lead to an improved outcome. Cetuximab plus RT has never been compared prospectively to CRT, which therefore remains the standard treatment for patients with locoregionally advanced SCCHN for whom surgery is not considered the optimal treatment, provided they can tolerate CRT. The addition of cetuximab to platinum-based chemotherapy prolongs survival in patients with recurrent or metastatic SCCHN. The combination of a platinum-based regimen and cetuximab should be considered as the standard first line regimen for patients who can tolerate this treatment.
Rapamycin derivatives reduce mTORC2 signaling and inhibit AKT activation in AML (2006)

The mTOR complex 2 (mTORC2) containing mTOR and rictor is thought to be rapamycin insensitive and was recently shown to regulate the prosurvival kinase AKT by phosphorylation on Ser473. We investigated the molecular effects of mTOR inhibition by the rapamycin derivatives (RDs) temsirolimus (CCI-779) and everolimus (RAD001) in acute myeloid leukemia (AML) cells. Unexpectedly, RDs not only inhibited the mTOR complex 1 (mTORC1) containing mTOR and raptor with decreased p70S6K, 4EPB1 phosphorylation, and GLUT1 mRNA, but also blocked AKT activation via inhibition of mTORC2 formation. This resulted in suppression of phosphorylation of the direct AKT substrate FKHR and decreased transcription of D-cyclins in AML cells. Similar observations were made in samples from patients with hematologic malignancies who received RDs in clinical studies. Our study provides the first evidence that rapamycin derivatives inhibit AKT signaling in primary AML cells both in vitro and in vivo, and supports the therapeutic potential of mTOR inhibition strategies in leukemias.
Optical properties of single-crystal sapphire fibers (1997)

Single-crystal sapphire fibers have been grown with the laser-heated pedestal-growth method with losses as low as 0.3 dB /m at 2.94 ?m. With the incorporation of a computer-controlled feedback system, fibers have been grown with less than +/-0.5 % diameter variation, or +/-1.5 ?m for a 300- ?m fiber. The losses in these fibers have been reduced further through a postgrowth anneal at 1000 degrees C in air, from 5.4 to 1.5 dB /m at 543 nm and from 0.4 -0.3 dB /m at 2.94 ?m. These fibers delivered 4.7 W at 10 Hz of Er:YAG laser power.
The Human Papillomavirus Type 16 E6 and E7 Oncoproteins Dissociate Cellular Telomerase Activity from the Maintenance of Telomere Length (1997)

The "high risk" subgroup of human papillomaviruses (e.g. HPV-16 and HPV-18) infect and induce tumors of mucosal epithelium. These neoplasms, which can progress to malignancy, retain and express the papillomavirus E6 and E7 oncogenes. In vitro, the E6 and E7 proteins associate with the cellular p53 and Rb proteins and interfere with their normal growth-regulatory functions. We report here that primary human keratinocytes transduced with the HPV-16 E6 gene, but not the E7 gene, express significant telomerase activity. However, despite this detectable enzymatic activity, E6-transduced cells continue to shorten their telomeres during in vitro passaging similar to control cells and to cells expressing the E7 and E6+E7 genes. At late passages, however, E7-transduced cells partially restore telomere length, although they lack detectable telomerase activity, demonstrating that E6-independent, telomerase-independent events mediate this change.