gebhart/patrepeval huggingface dataset:
Regulation of Epidermal Growth Factor Receptor Down-Regulation by UBPY-mediated Deubiquitination at Endosomes (2005)

Ligand-activated receptor tyrosine kinases undergo endocytosis and are transported via endosomes to lysosomes for degradation. This "receptor down-regulation" process is crucial to terminate the cell proliferation signals produced by activated receptors. During the process, ubiquitination of the receptors serves as a sorting signal for their trafficking from endosomes to lysosomes. Here, we describe the role of a deubiquitinating enzyme UBPY/USP8 in the down-regulation of epidermal growth factor (EGF) receptor (EGFR). Overexpression of UBPY reduced the ubiquitination level of EGFR and delayed its degradation in EGF-stimulated cells. Immunopurified UBPY deubiquitinated EGFR in vitro. In EGF-stimulated cells, UBPY underwent ubiquitination and bound to EGFR. Overexpression of Hrs or a dominant-negative mutant of SKD1, proteins that play roles in the endosomal sorting of ubiquitinated receptors, caused the accumulation of endogenous UBPY on exaggerated endosomes. A catalytically inactive UBPY mutant clearly localized on endosomes, where it overlapped with EGFR when cells were stimulated with EGF. Finally, depletion of endogenous UBPY by RNA interference resulted in elevated ubiquitination and accelerated degradation of EGF-activated EGFR. We conclude that UBPY negatively regulates the rate of EGFR down-regulation by deubiquitinating EGFR on endosomes.
Consensus Recommendations for Soft-Tissue Augmentation with Nonanimal Stabilized Hyaluronic Acid (Restylane) (2006)

The American Society for Aesthetic Plastic Surgery recently reported that there were nearly 12 million cosmetic procedures (2.1 million surgical and 9.7 million nonsurgical) performed in the United States in 2004. Almost 900,000 of the nonsurgical procedures were soft-tissue augmentation procedures using hyaluronic acid fillers. Restylane (Medicis Aesthetics, Inc., Scottsdale, Ariz.), nonanimal stabilized hyaluronic acid, was approved for use in the United States in December of 2003. Although the use of all fillers increased from 2003 to 2004, use of hyaluronic acid fillers increased nearly 700 percent. The dramatic increase in all cosmetic procedures reflects the growing trend, especially with increasing job competition, to maintain a youthful lifestyle and appearance. Basic recommendations for aesthetic use of Restylane were established based on short- and long-term efficacy and safety studies (Medicis Aesthetics, package insert). With the widespread and growing use of Restylane, a cross-sectional panel of experts with extensive clinical experience, including cosmetic dermatologists and surgical specialists (cosmetic, plastic, and ocular), convened to develop consensus guidelines for the use of Restylane. This supplement reviews the aesthetic affects of aging on the face, the role of fillers in facial soft-tissue volume replacement, and general principles for the use of Restylane, including patient comfort and assessment techniques. Specific recommendations for Restylane use in each potential target area, including type of anesthesia, injection techniques, volume for injection, use in combination with other procedures, and expected longevity of corrections, are provided. Techniques for optimizing patient outcomes and satisfaction and for minimizing and managing expected problems and potential complications are described.
Catalytic Hydroboration with Rhodium Complexes (1985)

The activation of CC double bonds for hydroboration may be achieved using rhodium complexes: e.g., the dioxaborole 1 undergoes preferential addition to the double bond when [CIRh(PPh3)3] is added to the reaction mixture.
A Naturally Occurring Rexinoid, Honokiol, Can Serve as a Regulator of Various Retinoid X Receptor Heterodimers (2012)

We investigated the properties of honokiol, a natural rexinoid, as a regulator of retinoid X receptor (RXR) heterodimers with various partner nuclear receptors (NRs), in comparison with those of the synthetic rexinoid bexarotene. Honokiol alone was hardly capable of activating peroxisome proliferator-activated receptor (PPAR) γ/RXR, RXR/liver X receptor (LXR), and RXR/vitamin D receptor (VDR) heterodimers, whereas it effectively potentiated their activation by agonists for the partner NRs of the RXR heterodimers. These findings were further supported by increased mRNA and protein levels for the respective NR target genes. Bexarotene alone activated PPARγ/RXR and RXR/LXR heterodimers, but not RXR/VDR heterodimers, and facilitated the activation of all three RXR heterodimers by the respective PPARγ, LXR, and VDR agonists. When the potencies of honokiol and bexarotene were compared, honokiol was able to serve as a subsidiary agonist in the activation of RXR heterodimers in a similar manner to bexarotene. However, it seemed to potentiate the activation of PPARγ/RXR heterodimers by the PPARγ agonist rosiglitazone more efficiently than bexarotene, and was a less potent RXR agonist than bexarotene. In conclusion, we have demonstrated that honokiol is a rexinoid that possesses distinct properties from bexarotene, and mainly has subsidiary roles in the activation of RXR heterodimers by potentiating the activation of RXR heterodimers by agonists for the partner NRs.
Promoting repair in multiple sclerosis: problems and prospects (2005)

Despite the increasing number of putative therapeutic targets, no treatment to achieve remyelination or neuroprotection has yielded positive clinical results in humans. Forging a link between basic biology and treatment of patients will require us to overcome several challenges, including assessment of efficacy of repair, improving tolerance to and delivery of neurotrophic factors, and better defining the indications for and limitations of transplantation.
Synthesis and Microbiological Evaluation of 2‐Acetanilido‐4‐arylthiazole Derivatives. (2006)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Secretion of a type II integral membrane protein induced by mutation of the transmembrane segment (1997)

Signal peptide/membrane anchor (SA) domains of type II membrane proteins initiate the translocation of downstream polypeptides across the endoplasmic reticulum (ER) membrane. In contrast with signal peptides, however, SA domains are not cleaved by signal peptidase and thus anchor the protein in the membrane. In the present study we have introduced mutations in the SA domain of neprilysin (neutral endopeptidase-24.11; NEP) to identify structural elements that would favour the processing of SA domains by signal peptidase. Mutants of full-length and truncated (without cytoplasmic domain) protein were constructed by substitution of the sequences SQNS, QQTT or YPGY for VTMI starting at position 15 of the NEP SA domain. In addition, a Pro residue was substituted for Thr at position 16 of the SA domain. The rationale for the use of these sequences was decided from our previous observation that substitution in the NEP SA domain of the sequence SQNS, which is polar and has alpha-helix-breaking potential, could promote SA domain processing under certain conditions (Roy, Chatellard, Lemay, Crine and Boileau (1993) J. Biol. Chem. 268. 2699-2704; Yang. Chatellard, Lazure, Crine and Boileau (1994) Arch. Biochem. Biophys. 315, 382-386). The QQTT sequence is polar but, according to secondary structure predictions, is compatible with the alpha-helix structure of the NEP SA domain. The YPGY sequence and single Pro residue are less polar and have alpha-helix-breaking potential. The predicted effects of these mutations on the structure of the NEP SA domain were confirmed by CD analysis of 42-residue peptides encompassing the hydrophobic segment and flanking regions. Wild-type and mutated proteins were expressed in COS-I cells and their fate (membrane-bound or secreted) was determined by immunoblotting and by endoglycosidase digestions. Our biochemical and structural data indicate that: (I) the cytosolic domain of NEP restricts the conformation of the SA domain because mutants not secreted in their full-length form are secreted in their truncated form; (2) alpha-helix-breaking residues are not a prerequisite for cleavage; (3) the presence, in close proximity to a putative signal peptidase cleavage site, of a polar sequence that maintains the alpha-helical structure of the SA domain is sufficient to promote cleavage. Furthermore pulse chase studies suggest that cleavage is performed in the ER by signal peptidase and indicate that cleavage is not a limiting step in the biosynthesis of the soluble form of the protein.
Complex, degradable polyester materials via ketoxime ether‐based functionalization: Amphiphilic, multifunctional graft copolymers and their resulting solution‐state aggregates (2010)

Abstract Degradable, amphiphilic graft copolymers of poly(ε‐caprolactone)‐ graft ‐poly(ethylene oxide), PCL‐ g ‐PEO, were synthesized via a grafting onto strategy taking advantage of the ketones presented along the backbone of the statistical copolymer poly(ε‐caprolactone)‐ co ‐(2‐oxepane‐1,5‐dione), (PCL‐ co ‐OPD). Through the formation of stable ketoxime ether linkages, 3 kDa PEO grafts and p ‐methoxybenzyl side chains were incorporated onto the polyester backbone with a high degree of fidelity and efficiency, as verified by NMR spectroscopies and GPC analysis (90% grafting efficiency in some cases). The resulting block graft copolymers displayed significant thermal differences, specifically a depression in the observed melting transition temperature, T m , in comparison with the parent PCL and PEO polymers. These amphiphilic block graft copolymers undergo self‐assembly in aqueous solution with the P(CL‐ co ‐OPD‐ co ‐(OPD‐ g ‐PEO)) polymer forming spherical micelles and a P(CL‐ co ‐OPD‐ co ‐(OPD‐ g ‐PEO)‐ co ‐(OPD‐ g ‐ p MeOBn)) forming cylindrical or rod‐like micelles, as observed by transmission electron microscopy and atomic force microscopy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3553–3563, 2010
Inflammasome-dependent Caspase-1 Activation in Cervical Epithelial Cells Stimulates Growth of the Intracellular Pathogen Chlamydia trachomatis (2009)

Inflammasomes have been extensively characterized in monocytes and macrophages, but not in epithelial cells, which are the preferred host cells for many pathogens. Here we show that cervical epithelial cells express a functional inflammasome. Infection of the cells by Chlamydia trachomatis leads to activation of caspase-1, through a process requiring the NOD-like receptor family member NLRP3 and the inflammasome adaptor protein ASC. Secretion of newly synthesized virulence proteins from the chlamydial vacuole through a type III secretion apparatus results in efflux of K(+) through glibenclamide-sensitive K(+) channels, which in turn stimulates production of reactive oxygen species. Elevated levels of reactive oxygen species are responsible for NLRP3-dependent caspase-1 activation in the infected cells. In monocytes and macrophages, caspase-1 is involved in processing and secretion of pro-inflammatory cytokines such as interleukin-1beta. However, in epithelial cells, which are not known to secrete large quantities of interleukin-1beta, caspase-1 has been shown previously to enhance lipid metabolism. Here we show that, in cervical epithelial cells, caspase-1 activation is required for optimal growth of the intracellular chlamydiae.
Structural and electrical properties of granular metal films (1975)

Abstract Granular metal films (50–200,000 Å thick) were prepared by co-sputtering metals (Ni, Pt, Au) and insulators (SiO2, Al2O3), where the volume fraction of metal, x, was varied from x = 1 to x = 0.05. The materials were characterized by electron micrography, electron and X-ray diffraction, and measurements of composition, density and electrical resistivity at electric fields ε up to 106 V/cm and temperatures T in the range of 1.3 to 291 K. In the metallic regime (isolated insulator particles in a metal continuum) and in the transition regime (metal and insulator particles in a metal continuum) and in the transition regime (metal and insulator labyrinth structure) the conduction is due to percolation with a percolation threshold at x⋍0.5. Tunnelling measurements on superconductor-insulator-granular metal junctions reveals that the transition from the metallic regime to the dielectric regime (10–50 Å size isolated metal particles in an insulator continuum) is associated with the breaking up of a metal continuum into isolated metal particles. In the dielectric regime the temperature dependence of the low-field resistivity is given by ρL = ρo exp [2√(C/kT)], and the field dependence of the high-field, low-temperature resistivity is given by ρH = ρ∞ exp (εo/ε), where ρo, ρ∞, C, and εo are material constants. A simple theory based on the assumption that the ratio s/d (d-metal particle size and s-separation between particles) is a function only of composition yields expressions for ρ(ε, T) in excellent agreement with experiment. Furthermore, the theory predicts the experimental finding that the resistivity can be expressed in terms of a universal function of the reduced variables kT/C and ε/εo. The inter-relationship between all the important physical properties of granular metals and their structure is also discussed.
The human interleukin-2 receptor: insights into subunit structure and growth signal transduction. (1990)

Lymphokine-dependent T cell proliferation is regulated in part by the cell surface expression of high affinity interleukin-2 receptors (IL-2R). The functional, high affinity form of the IL-2 receptor is comprised of two ligand binding components, IL-2R alpha (Tac, p55) and IL-2R beta (p70/75). In the absence of the other subunit, IL-2R alpha and IL-2R beta bind ligand with only low or intermediate affinity, respectively. The inducible and transient expression of IL-2R alpha regulates the display of high affinity receptors, while IL-2R beta appears to contribute importantly to growth signal transduction. Although the primary structure of both receptor chains has now been elucidated, the mechanism of growth signal transduction through the high affinity IL-2R remains undefined. Of note, IL-2R beta belongs to a novel family of cytokine receptors including the binding proteins for IL-3, IL-4, IL-6, erythropoietin, and granulocyte-macrophage colony-stimulating factor. These various receptors may well utilize a common intracellular signalling pathway.
Altering the RNA binding specificity of a translational repressor. (1994)

The coat proteins of RNA phages MS2 and GA are specific RNA-binding proteins which function to encapsidate viral RNA and to translationally repress synthesis of the viral replicase. The two proteins have highly homologous amino acid sequences, yet they show different RNA binding specificities, recognizing RNA stem-loop structures which differ primarily in the nucleotide sequences of their loops. We sought to convert MS2 coat protein to the RNA binding specificity of GA through the introduction of GA-like amino acid substitutions into the MS2 coat protein RNA-binding site. The effects of the mutations were determined by measuring the affinity of the coat protein variants for RNA in vitro and by measuring translational repression in vivo. We found five substitutions that affect RNA binding. One dramatically reduces binding of MS2 coat protein to both operators. Three others compensate for this defect by nonspecifically strengthening the interaction. Another substitution accounts for the ability to recognize the differences in the RNA loop sequence.
Complications associated with endocapsular balloon implantation in rabbit eyes (1994)

After phacoemulsifying the lens in six rabbit eyes through a 1.3 mm anterior capsule opening, we implanted a silicone balloon in the capsular bag and filled it with liquid silicone. The eyes were enucleated nine to 21 months postoperatively, embedded in paraffin, stained with toluidine blue, and examined by stereoscopic and light microscopy. We looked at the postoperative complications primarily. All balloons were securely fixated within the capsule. Surface wrinkles were observed in two balloons. The injected silicone remained transparent. None of the lens capsules was completely transparent, although all remained relatively clear. Retrocorneal membranes were produced in one eye in which the silicone leaked.
A Potent Cross-Clade Neutralizing Human Monoclonal Antibody against a Novel Epitope on gp41 of Human Immunodeficiency Virus Type 1 (2001)

We have established a panel of human monoclonal antibodies against human immunodeficiency virus type 1 (HIV-1). The antibodies 2F5 and 2G12 have been identified to be two of the most potently in vitro neutralizing antibodies against HIV-1. Here we report on a further antibody, 4E10, of similar in vitro neutralizing potency. 4E10 binds to a novel epitope C terminal of the ELDKWA sequence recognized by 2F5, which has been so far the only described broadly neutralizing anti-gp41 antibody. Both 4E10 and 2F5 bind only weakly to infected cells compared with gp120-specific 2G12 and polyclonal anti-HIV-1 immunoglobulin (HIVIG), but show potent in vitro neutralizing properties. 4E10 neutralizes potently not only tissue culture-adapted strains but also primary isolates of different clades, including A, B, C, D, and E. Viruses that were found to be resistant to 2F5 were neutralized by 4E10 and vice versa; none of the tested isolates was resistant to both anti-gp41 antibodies. This confirms that the region recognized by 2F5 and 4E10 is essential for viral infectivity and may be important for vaccine design. Moreover, our results suggest that 4E10 should be further investigated for passive anti-HIV immunotherapy.
Characterization of the role of IL‐6 in the progression of prostate cancer (1999)

BACKGROUND We recently identified IL-6, a pleiotropic cytokine implicated in the neoplastic process of a variety of neoplasms, as a mediator of prostate cancer morbidity. In the present study, we investigated the expression of members of the IL-6 supergene family and related cytokines and the potential role of IL-6 in prostate cancer growth regulation. METHODS Five established human prostate cancer cell lines were screened by ELISA for production of granulocyte colony-stimulating factor (G-CSF), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), tumor necrosis factor (TNF), interleukin-1 (IL-1), and granulocyte macrophage colony-stimulating factor (GM-CSF). Expression of the ligand-binding component of the IL-6 receptor, IL-6Rp80, was evaluated by ELISA and RT-PCR. Sequential immunoprecipitation and immunoblotting were performed to assay for expression of the signal-transducing component of the IL-6 receptor, gp130. The effects of IL-6 on cell growth were assessed by MTT assays. RESULTS The three hormone-refractory cell lines, DU-145, TSU, and PC-3, secreted distinct combinations of cytokines (DU-145: IL-6, GM-CSF; TSU: IL-6, LIF; PC-3: IL-6, G-CSF, LIF, IL-1, GM-CSF), each uniformly expressing IL-6. In contrast, neither of the two hormone-dependent cell lines, LNCaP-ATCC and LNCaP-GW, secreted significant quantities of any of the cytokines analyzed. None of the cell lines secreted detectable quantities of OSM, CNTF, or TNF. All cell lines, irrespective of hormone status, expressed both Il-6Rp80 and gp130. Addition of IL-6 in vitro inhibited growth of hormone-dependent cells, but had no effect on hormone-refractory lines. Anti-IL-6 neutralizing antibody inhibited growth of hormone-refractory cells. CONCLUSIONS IL-6 appears to undergo a functional transition from paracrine growth inhibitor to autocrine growth stimulator during progression of prostate cancer to the hormone-refractory phenotype. Prostate 38:199–207, 1999. © 1999 Wiley-Liss, Inc.
Small-Dose Ketamine Improves the Postoperative State of Depressed Patients (2002)

NMDA receptor antagonists are reported to be effective for improving depression. It remains unclear whether ketamine, which is an NMDA receptor antagonist, postoperatively affects the psychological state in depressed patients. We investigated the effect of 1.0 mg/kg of ketamine on postoperative outcomes in depressed patients.
Structure of boromycin (1971)

Abstract The structure II of boromycin C 45 H 74 BNO 15 ( cf. [2]) has been established by combination of chemical evidence with X‐ray analysis. The antibiotic is a D‐valine ester of a Böeseken ‐complex of boric acid with a macrodiolide of a new type.
Site-directed Mutagenesis of Cysteine Residues in the Pro Region of the Transforming Growth Factor β1 Precursor (1989)

Three cysteine residues are located in the pro region of the transforming growth factor 81 (TGF-81) precursor at amino acid positions 33,223, and 225.Previous studies (Gentry, L. E., Lioubin, M. N., Purchio, A. F., and Marquardt,
Thymic Dendritic Cells (2005)

This chapter contains sections titled: Thymic Dendritic Cells Localisation and Isolation of Thymic DC Pickup of Antigens by Thymic DC Subtypes of Thymic DC Major Thymic cDC Population Minor Thymic cDC Population Thymic pDC Maturation State and Antigen Processing Capacity of Thymic DC Cytokine Production by Thymic DC DC of the Human Thymus Turnover Rate and Lifespan of the Thymic DC Endogenous versus Exogenous Sources of Thymic DC Lineage Relationship and Differentiation Pathways of Thymic cDC Lineage Relationships and Developmental Pathways of Thymic pDC Thymic cDC do not Mediate Positive Selection Thymic cDC and Negative Selection Role of pDC in the Thymus
Switching Time in Junction Diodes and Junction Transistors (1954)

The time in which a junction diode may be switched from forward to reverse conduction is of great importance in computing networks. By considering the behavior of the minority carriers in a diode In a representative switching circuit an approximate solution for the switching transient may be derived. The transient is separated into two phases: first, one of constant current, where the flow is limited by the external resistance, and second, a "collection" phase, where the current decays at a rate determined by the minority carrier lifetime and the dimensions of the diode. A critical parameter in the solution is the ratio of the short-circuit reverse current to the forward current before switching. The mathematical treatment is a boundary value solution of the minority carrier diffusion equations which is accomplished by the use of Laplace transformations. The duration of the two phases of current flow is determined for a planar junction, a hemispherical junction, and for a planar junction with junction-to-contact distance small compared to a diffusion length. The last treatment is extended to the junction transistor and the behavior of the collector current is calculated. The general results indicate that for a given nority carrier lifetime the last two of the three diode structures will give the smallest switching times. In addition it is found generally that the time is minimized by decreasing lifetime and increasing the ratio of reverse to forward current.