gebhart/patrepeval huggingface dataset:
Sir- and Silencer-Independent Disruption of Silencing in Saccharomyces by Sas10p (1998)

Abstract A promoter fusion library of Saccharomyces cerevisiae genes was used to exploit phenotypes associated with altered protein dosage. We identified a novel gene, SAS10, by the ability of Sas10p, when overproduced, to disrupt silencing. The predicted Sas10p was 70,200 kD and strikingly rich in charged amino acids. Sas10p was exclusively nuclear in all stages of the cell cycle. Overproduction of Sas10p caused derepression of mating type genes at both HML and HMR, as well as of URA3, TRP1, and ADE2 when inserted near a telomere or at HMR or the rDNA locus. Repressed genes not associated with silenced chromatin were unaffected. Sas10p was essential for viability, and the termination point following Sas10p depletion was as large budded cells. Remarkably, Sas10p overproduction disrupted silencing even under conditions that bypassed the requirement for Sir proteins, ORC, and Rap1p in silencing. These data implied that Sas10p function was intimately connected with the structure of silenced chromatin.
Sigma Receptor Ligands: Possible Application as Therapeutic Drugs and as Radiopharmaceuticals (2006)

Sigma receptors are classified into sigma(1) and sigma(2) subtypes. These subtypes display a different tissue distribution and a distinct physiological and pharmacological profile in the central and peripheral nervous system. The characterization of these subtypes and the discovery of new specific sigma receptor ligands demonstrated that sigma receptors are novel targets for the therapeutic treatment of neuropsychiatric diseases (schizophrenia, depression, and cognition), brain ischemia, and cocaine addiction. Furthermore, imaging of sigma(1) receptors in the human brain using specific PET radioligands has started. In addition, the two sigma receptor subtypes are also expressed on tumor cells, where they could be of prognostic relevance. The ability of sigma(2) receptor agonists to inhibit tumor cell proliferation through mechanisms that might involve apoptosis, intracellular Ca(2+), and sphingolipids has promoted the development of sigma(2) receptor agonists as novel therapeutic drugs for treating cancer. Consequently, sigma(2) receptor ligands have been demonstrated to be potentially useful tumor imaging ligands. In this article, we focus on the sigma receptor ligands as therapeutic agents and as radiopharmaceuticals.
Quality of Life in Long-Term, Disease-Free Survivors of Breast Cancer: a Follow-up Study (2002)

Long-term, disease-free breast cancer survivors reported high levels of functioning and QOL many years after primary treatment. However, past systemic adjuvant treatment was associated with poorer functioning on several dimensions of QOL. This information may be useful to patients and physicians who are engaging in discussion of the risks and benefits of systemic adjuvant therapy.
Involvement of lipid rafts in the localization and dysfunction effect of the antitumor ether phospholipid edelfosine in mitochondria (2011)

Lipid rafts and mitochondria are promising targets in cancer therapy. The synthetic antitumor alkyl-lysophospholipid analog edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) has been reported to target lipid rafts. Here, we have found that edelfosine induced loss of mitochondrial membrane potential and apoptosis in human cervical carcinoma HeLa cells, both responses being abrogated by Bcl-x(L) overexpression. We synthesized a number of new fluorescent edelfosine analogs, which preserved the proapoptotic activity of the parent drug, and colocalized with mitochondria in HeLa cells. Edelfosine induced swelling in isolated mitochondria, indicating an increase in mitochondrial membrane permeability. This mitochondrial swelling was independent of reactive oxygen species generation. A structurally related inactive analog was unable to promote mitochondrial swelling, highlighting the importance of edelfosine molecular structure in its effect on mitochondria. Raft disruption inhibited mitochondrial localization of the drug in cells and edelfosine-induced swelling in isolated mitochondria. Edelfosine promoted a redistribution of lipid rafts from the plasma membrane to mitochondria, suggesting a raft-mediated link between plasma membrane and mitochondria. Our data suggest that direct interaction of edelfosine with mitochondria eventually leads to mitochondrial dysfunction and apoptosis. These observations unveil a new framework in cancer chemotherapy that involves a link between lipid rafts and mitochondria in the mechanism of action of an antitumor drug, thus opening new avenues for cancer treatment.
Administration of R24 monoclonal antibody and low-dose interleukin 2 for malignant melanoma. (1997)

R24 is a monoclonal antibody that recognizes the disialoganglioside GD3 expressed on the surface of malignant melanoma cells. Once bound, it can mediate destruction of these cells through both complement-mediated lysis and antibody-dependent cellular cytotoxicity. Agents such as interleukin 2 (IL-2), which can augment effector cell function and promote destruction of antibody-coated tumor cells, might produce improved antitumor responses when combined with R24. In this series, we evaluated the combination of R24 and IL-2 in a Phase 1b study in patients with metastatic melanoma. Twenty-eight patients with metastatic melanoma were entered into the protocol at two institutions. Patients received 8 weeks of IL-2 by continuous i.v. infusion at a dose (4.5 x 10(5) Amgen units/m2/day) designed to selectively expand natural killer (NK) cells. In weeks 5 and 6, patients received R24 for a total of four doses. Twenty-four h after each R24 infusion, patients received a 2-h bolus dose of IL-2 to help promote activity of NK effectors against antibody-coated melanoma targets. Additional IL-2 boluses were administered in weeks 7 and 8. Doses were escalated through two bolus doses of R24 (5 or 15 mg/m2) and two bolus doses of IL-2 (2.5 or 5.0 x 10(5) units/m2). Although one patient experienced severe capillary leak syndrome during IL-2, therapy was otherwise well tolerated. At the higher dose level of R24, two of four patients experienced transient but severe abdominal and chest discomfort, necessitating dose reduction. One patient with ocular melanoma and liver metastases had a partial response. Two additional patients had minor responses. A dramatic increase in NK cell number was noted as a result of treatment, as was augmentation of cytolytic activity against cultured NK-sensitive targets. Antibody-dependent cellular cytotoxicity against cultured melanoma cells in the presence of exogenous R24 or in the presence of serum obtained from patients following R24 infusion also increased during treatment. Our experience indicates that R24 and low-dose IL-2 can be safely combined in patients with metastatic melanoma and that this combination can promote destruction of cultured melanoma cells. The clinical activity of this combination against ocular melanoma may merit further investigation.
Vascular access thrombosis: etiology and prevention. (1999)

Vascular access thrombosis has been the Achilles heel of patients with end-stage renal disease since the inception of maintenance hemodialysis. Although many factors have been implicated in the etiology of access thrombosis, data indicate that the primary risk factors include an increased use of synthetic polytetrafluoroethylene grafts, lack of surgical expertise in access construction, advanced age, systolic hypotension, and high levels of serum lipoprotein (a). The occurrence and severity of access problems can be modified by ongoing nurse monitoring and prompt intervention to proactively correct evolving problems.
Representing Internet Protocol version 6 (IPv6) Addresses in the Domain Name System (DNS) (2002)

This document clarifies and updates the standards status of RFCs that define direct and reverse map of IPv6 addresses in DNS. This document moves the A6 and Bit label specifications to experimental status.
Evaluating grapheme-to-phoneme converters in automatic speech recognition context (2012)

This paper deals with the evaluation of grapheme-to-phoneme (G2P) converters in a speech recognition context. The precision and recall rates are investigated as potential measures of the quality of the multiple generated pronunciation variants. Very different results are obtained whether or not we take into account the frequency of occurrence of the words. Since G2P systems are rarely evaluated on a speech recognition performance basis, the originality of this paper consists in using a speech recognition system to evaluate the G2P pronunciation variants. The results show that the training process is quite robust to some errors in the pronunciation lexicon, whereas pronunciation lexicon errors are harmful in the decoding process. Noticeable speech recognition performance improvements are achieved by combining two different G2P converters, one based on conditional random fields and the other on joint multigram models, as well as by checking the pronunciation variants of the most frequent words.
Clinical analysis of 98 pregnant women with gestation diabetes mellitus (2010)

Objective: To understand whether the control of glucose level can influence the pregnant women with gestation diabetes mellitus(GDM) and neonate.Methods: 98 pregnant women with gestation diabetes mellitus(GDM) were divided into two groups,68 persons in Group A were with GDM by antepartum screening diagnosis and their glucose level were satisfactorily controlled,while the other 30 persons in Group B received no treatment until being admitted into hospital and their glucose level failed to reach the satisfactory point.Then,the pregnant outcome and delivery situation were compared between the two groups.Results: There were statistics differences between the two groups,the occurrence of hypertensive disorders,premature rupture of membrane,polyhydramnios,cesarean section, premature delivery,fetal macrosomia and neonatal nypoglycemia in patients of Group A was remarkably lower than those in Group B(P0.05).Conclusions: The timely diagnosis and efficient treatment of GDM can reduce the incidence of complications of pregnant women with GDM and neonate.
Freeze-Drying of tert-Butyl Alcohol/Water Cosolvent Systems: Effects of Formulation and Process Variables on Residual Solvents (1998)

The objective of this study was to identify significant formulation and processing variables affecting levels of tert-butyl alcohol (TBA) and isopropyl alcohol (IPA) in freeze-dried solids prepared from TBA/water cosolvent systems. The variables examined were the physical state of the solute (crystalline vs amorphous), initial TBA concentration, freezing rate, cake thickness, and the temperature and duration of secondary drying. Sucrose and glycine were used as models for noncrystallizing and crystallizing solutes, respectively. The TBA concentration above which eutectic crystallization takes place was determined by differential scanning calorimetry. Model formulations were subjected to extremes of freezing rate by either dipping in liquid nitrogen or by slowly freezing on the shelf of a freeze-dryer. Dynamics of solvent loss during secondary drying was determined by withdrawing samples as a function of time at different shelf temperatures using a thief system. On the basis of these studies, the most important determinant of residual TBA level is the physical state of the solute. Freeze-dried glycine contained very low levels of residual TBA (0.01-0.03%) regardless of freezing rate or initial TBA concentration. For freeze-dried sucrose, residual TBA levels were approximately 2 orders of magnitude higher and were significantly affected by initial TBA concentration and freezing rate. For the sucrose/TBA/water system, relatively low residual TBA levels were obtained when the initial TBA level was above the threshold concentration for eutectic crystallization of TBA, whereas samples freeze-dried from solutions containing TBA concentrations below this threshold contained significantly higher levels of TBA. Residual IPA levels increased continuously with initial concentration of TBA in the sucrose/TBA/water system. Formulations of sucrose/TBA/water which were frozen rapidly contained residual TBA levels which were approximately twice those measured in the same formulation after slow freezing and drying under the same conditions. For the sucrose/TBA/water system, the temperature and time of secondary drying had only minimal influence on residual TBA in the freeze-dried solid. At low initial TBA concentrations (2%), residual TBA increases with increased cake thickness, perhaps because of the influence of depth of fill on effective freezing rate.
Androgenic Regulation of NO Availability in Rat Penile Erection (1997)

Prior studies from this laboratory, using untreated castrated (CASTRATE) rats and testosterone-treated castrated (TESTO) rats, have shown that the magnitude of the intracavernosal pressure increase during erection is androgen dependent. Studies from this and other laboratories have also presented evidence suggesting that penile erection is mediated principally by nitric oxide (NO). The present report was designed to confirm that androgens maintain the availability of cavernosal NO and to determine if this androgenic action is exerted at the genomic level modulating the expression of the neuronal form of the nitric oxide synthase gene (nNOS). The results showed that administration of supplemental L-arginine failed to augment the erectile response in either group, suggesting that substrate availability is not a cause of the reduced response in CASTRATE animals. Inhibition of NO synthesis with a nitro-arginine competitive inhibitor of nitric oxide synthase enzyme protein (NOS) resulted in strong inhibition of erection in both TESTO and CASTRATE rats. When given in conjunction with ganglionic stimulation to induce erection, the NO releasing drug, sodium nitro-prusside (SNP), increased intracavernosal pressure in CASTRATE rats but not in TESTO rats, suggesting a deficiency of the available NO in CASTRATE-animals. Finally, reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that mRNA levels for the enzyme nNOS in the penis were greater in TESTO animals than in CASTRATE rats. These results support the hypothesis that androgens mediate the erectile response in the rat penis by stimulating the expression of the neuronal isoform of nitric oxide synthase, thus maintaining an adequate supply of NO.
Highly Disordered Polymer Field Effect Transistors: N-Alkyl Dithieno[3,2-b:2′,3′-d]pyrrole-Based Copolymers with Surprisingly High Charge Carrier Mobilities (2008)

A series of novel electroactive and photoactive conjugated copolymers based on N-alkyl dithieno[3,2-b:2',3'-d]pyrroles (DTP) and thiophene (TH) units (DTP-co-THs) were synthesized using a Stille coupling reaction and exhibited molecular weights of 1.6 x 10(4) to 5.0 x 10(4) g/mol. The incorporation of soluble substituted thiophenes and planar DTP units resulted in low band gap, highly conductive polymers. DTP-co-THs exhibited excellent solubility in common organic solvents and formed high-quality films. Optical characterization revealed that the band gaps of DTP-co-THs were between 1.74 and 2.00 eV, lower than regioregular poly(3-alkylthiophenes). Electrochemical characterization showed that the HOMO energy levels of DTP-co-THs are between -4.68 and -4.96 eV. When doped, DTP-co-THs exhibited high conductivities up to 230 S/cm with excellent stability. The different thiophene substituent patterns' effect on the polymers' optical and electronic properties was then examined by density functional theory computations. The microstructure and surface morphologies of poly(2,6-(4-dodecyl-4H-bisthieno[3,2-b:2',3'-d]pyrrole)-random-2,5-(3-dodecylthiophene)) (P4) and poly(2-(4,4'-didodecyl-2,2'-bithiophen-5-yl)-4-octyl-4H-bisthieno[3,2-b:2',3'-d]pyrrole) (P6) thin films were studied by X-ray diffraction and atomic force microscopy. As-cast P4 and P6 thin films exhibited poorly defined, randomly ordered lamellar structure that improved significantly after thermal annealing. Field effect transistor devices fabricated from P4 and P6 showed typical p-channel transistor behavior. Interestingly, the mobilities of as-cast, less ordered samples were much higher than those observed after annealing. The highest values of maximum and average mobilities were observed for the polymer P6 as-cast (0.21 and 0.13 cm(2) V(-1) s(-1), respectively). One of our goals was to test the idea that high mobility and excellent electrical and structural reproducibility could perhaps be achieved by the creation of amorphous pi-conjugated materials that could possess long arrange pi connectivity on the microscopic scale. The results of these studies strongly suggest that the presence of highly ordered microcrystalline structures in thin films of organic semiconductors is not necessary for excellent performance of organic transistors.
Antigenicity of polypeptides (poly alpha amino acids): calcium-dependent and independent antibodies. (1970)

It has been shown that sheep antisera against negatively charged synthetic polymers of amino acids such as poly (L-glu60-L-ala30-L-tyr10)n of high glutamic acid content contain two populations of antibodies one of which requires calcium (“Ca++ dependent”) for reaction to occur. The Ca++-dependent antibodies are directed against immunogenic determinants created by the reaction of Ca++ with glutamyl residues which changes the conformation of the polymer and thereby creates the new determinants. The reaction of the specific polymer with this antibody is maximal at 0.008 M Ca++. Dissociation of the polymer-Ca++-antibody complex can be accomplished by removal of Ca++ with EDTA, citrate or oxalate or by washing the antigen-antibody precipitate with phosphate-buffered saline. Dilution of the antiserum in non-Ca++-containing diluents, which in effect lowers the Ca++ concentration, reduces precipitation of the antibody. This loss can be reversed by addition of Ca++ to the diluting buffer. The amounts of these two populations of antibodies vary from animal to animal within any species. No Ca++-dependent antibody was found with the polymers of slight negative or neutral charge or against several protein antigens. Peptide maps (finger prints) of these two kinds of purified antibody (both 7S IgG) revealed no significant differences.
Effects of Amino Acid Variations in Recombinant <i>Der f</i> ll on Its Human IgE and Mouse IgG Recognition (1994)

Amino acid sequencing of the major mite allergen Der fII purified from mite body extract revealed that it is a mixture of at least two variants. Substitutions were found only at positions in which amino acid variations were predicted from the nucleotide sequences of three cloned cDNAs. When cDNAs corresponding to the three variants were expressed in Escherichia coli, Der fII proteins were produced as inclusion bodies. Denaturation and renaturation with urea converted recombinant Der fII into a protein with three intramolecular disulfide bonds (Cys8-Cys119, Cys21-Cys27, and Cys73-Cys78), which were identical to those previously identified in native Der fII. All the variants, including native Der fII, were equally recognized by human IgE antibodies from 14 different sera of mite-allergic patients. These results suggested that recombinant Der fII proteins assumed a conformation identical to that of the native Der fII and that all the Der fII variants acted as allergens. This result also suggested that IgE antibody binds to the region where there were no amino acid variations. The binding ability of the monoclonal antibody (mAb) 18G8 for the variant clones 1, 2, and 11 Der fII was almost the same. However, mAb 15E11 bound to clone 1 Der fII more efficiently than to clones 2 and 11, whereas mAb 13A4 recognized clone 2 Der fII as the most preferable antigen. This suggested that these antibodies recognized the region of amino acid variations. The stability of Der fII variants was analyzed by measuring their IgE antibody binding activity after heating, freezing, or acid treatment, and was analyzed by resistance to trypsin digestion.(ABSTRACT TRUNCATED AT 250 WORDS)
Composition and density of bacterial biofilms determine larval settlement of the polychaete Hydroides elegans (2003)

MEPS Marine Ecology Progress Series Contact the journal Facebook Twitter RSS Mailing List Subscribe to our mailing list via Mailchimp HomeLatest VolumeAbout the JournalEditorsTheme Sections MEPS 260:161-172 (2003) - doi:10.3354/meps260161 Composition and density of bacterial biofilms determine larval settlement of the polychaete Hydroides elegans Shuyi Huang, Michael G. Hadfield* Kewalo Marine Laboratory, University of Hawaii, 41 Ahui Street, Honolulu, Hawaii 96813, USA *Corresponding author. Email: hadfield@hawaii.edu ABSTRACT: Larvae of the polychaete worm Hydroides elegans settle and metamorphose in response to marine biofilms. Phylogenetic relationships among 4 marine-biofilm bacterial species identified by 16S rDNA sequences were not predictive of their inductive capacity. Two bacterial species separated by a genetic distance of 30% shared the greatest capacity for inducing metamorphosis in H. elegans. Two bacterial strains with only a 3% divergence in 16S rRNA gene sequences were very different; one strain induced metamorphosis strongly while the other one did not. The percent of larvae that metamorphosed correlated positively with bacterial density in either natural biofilms or biofilms composed of a single bacterial species. When results of tests across 4 bacterial species were compared, the most inductive bacterial species was effective in much lower biofilm densities than weakly or non-inductive bacteria. Evidence presented here indicates that the cue that triggers settlement and metamorphosis in larvae of H. elegans is not unique to a single bacterial taxon and is likely to be an insoluble, surface-bound material. KEY WORDS: Biofilm bacteria · Larval settlement · Metamorphosis · Hydroides elegans Full text in pdf format PreviousNextExport citation RSS - Facebook - Tweet - linkedIn Cited by Published in MEPS Vol. 260. Online publication date: September 30, 2003 Print ISSN: 0171-8630; Online ISSN: 1616-1599 Copyright © 2003 Inter-Research.
The Role of Complement in the Mechanism of Action of Rituximab for B-Cell Lymphoma: Implications for Therapy (2008)

Rituximab, a genetically engineered chimeric monoclonal antibody specifically binding to CD20, was the first antibody approved by the U.S. Food and Drug Administration for the treatment of cancer. Rituximab significantly improves treatment outcome in relapsed or refractory, low-grade or follicular B-cell non-Hodgkin's lymphoma (NHL). However, there are also some challenges for us to overcome: why approximately 50% of patients are unresponsive to rituximab in spite of the expression of CD20, and why some responsive patients develop resistance to further treatment. Although the antitumor mechanisms of rituximab are not completely understood, several distinct antitumor activities of rituximab have been suspected, including complement-dependent cytotoxicity (CDC), antibody-dependent cellular cytotoxicity (ADCC), apoptosis, and direct growth arrest. To counteract resistance to rituximab therapy, several strategies have been developed to: (a) augment the CDC effect by increasing CD20 expression, heteroconjugating rituximab to cobra venom factor and C3b, and inhibiting membrane complement regulatory protein, especially CD59, function; (b) enhance the ADCC effect through some immunomodulatory cytokines and CR3-binding beta-glucan; and (c) reduce the apoptotic threshold or induce apoptotic signaling on the tumor. Extensive studies indicate that rituximab combined with these approaches is more effective than a single rituximab approach. Herein, the mechanism of action of and resistance to rituximab therapy in B-cell NHL, in particular, the involvement of the complement system, are extensively reviewed.