gebhart/patrepeval huggingface dataset:
Disruption of cell-cell adhesion enhances antibody-dependent cellular cytotoxicity: implications for antibody-based therapeutics of cancer. (2002)

Resistance to antibody-based anticancer approaches has become of considerable interest because of the rapidly growing clinical use of several different monoclonal antibodies as therapeutic agents, coupled with the recent finding that their efficacy may be attributable in part to their participation in host antibody-dependent cellular cytotoxicity. In this proof-of-concept study, we demonstrate the novel ability of an antiadhesive antibody (SHE78-7), targeted at the potent homophilic cell adhesion molecule E-cadherin, to play a dual role as participant in, and sensitizing agent for, host immune-mediated antitumor activity. SHE78-7 disrupted preformed multicellular aggregates (spheroids) of HT29 colon carcinoma cells both in vitro and in vivo in an ascites tumor xenograft model, but had no direct antitumor effect in vitro. In vivo, however, i.p. injection of SHE78-7 significantly prolonged the survival of nude mice carrying established i.p. HT29 xenografts, most notably when injections were given biweekly. This antitumor effect was dependent on the antiadhesive effect of SHE78-7 and could be effectively recapitulated via treatment with a combination of nondisruptive anti-hMHC-I antibodies, capable of recruiting an F(c)-mediated immune response but ineffective as a monotherapy and antiadhesive F(ab')(2) fragments of SHE78-7. Furthermore, additional therapy experiments using such F(ab')(2) fragments, or mice lacking activating F(c)gammaRIII receptors or inhibitory F(c)gammaRIIB, unequivocally indicated a role for host antibody-dependent cellular cytotoxicity, mediated by F(c)gammaRIII and negatively regulated by F(c)gammaRIIB. Taken together, the results suggest a possible means of improving antibody-based therapies of cancer, namely targeting antigens, selectively expressed or up-regulated by target cancer cells, which mediate cell-cell adhesive functions.
Hydroxyapatite Cement in Craniofacial Reconstruction (2005)

Hydroxyapatite cements are safe in craniofacial reconstruction. The highest risk of implant infection comes from reconstruction in the area of the frontal sinus, immediately beneath coronal incisions, and in patients who receive postoperative radiation treatment. Based on our results, there does appear to be a statistically significant difference in rates of infection and foreign body reaction between the different types of hydroxyapatite cement. We would not recommend implantation of this material in contact with the frontal sinus. Caution should be exercised when it is placed directly beneath an incision or in patients receiving postoperative radiation, particularly if a boost dose is given.
Construction of an Escherichia coli-Rhodococcus shuttle vector and plasmid transformation in Rhodococcus spp (1988)

A plasmid transformation system for Rhodococcus sp. strain H13-A was developed by using an Escherichia coli-Rhodococcus shuttle plasmid constructed in this study. Rhodococcus sp. strain H13-A contains three cryptic indigenous plasmids, designated pMVS100, pMVS200, and pMVS300, of 75, 19.5, and 13.4 kilobases (kb), respectively. A 3.8-kb restriction fragment of pMVS300 was cloned into pIJ30, a 6.3-kb pBR322 derivative, containing the E. coli origin of replication (ori) and ampicillin resistance determinant (bla), as well as a Streptomyces gene for thiostrepton resistance, tsr. The resulting 10.1-kb recombinant plasmid, designated pMVS301, was isolated from E. coli DH1(pMVS301) and transformed into Rhodococcus sp. strain AS-50, a derivative of strain H13-A, by polyethylene glycol-assisted transformation of Rhodococcus protoplasts and selection for thiostrepton-resistant transformants. Thiostrepton-resistant transformants were also ampicillin resistant and were shown to contain pMVS301, which was subsequently isolated and transformed back into E. coli. The cloned 3.8-kb fragment of Rhodococcus DNA in pMVS301 contains a Rhodococcus origin of replication, since the hybrid plasmid was capable of replication in both genera. The plasmid was identical in E. coli and Rhodococcus transformants as determined by restriction analysis and was maintained as a stable, independent replicon in both organisms. Optimization of the transformation procedure resulted in transformation frequencies in the range of 10(5) transformants per micrograms of pMVS301 DNA in Rhodococcus sp. strain H13-A and derivative strains. The plasmid host range extends to strains of Rhodococcus erythropolis, R. globulerus, and R. equi, whereas stable transformants were not obtained with R. rhodochrous or with several coryneform bacteria tested as recipients. A restriction map demonstrated 14 unique restriction sites in pMVS301, some of which are potentially useful for molecular cloning in Rhodococcus spp. and other actinomycetes. This is the first report of plasmid transformation and of heterologous gene expression in a Rhodococcus sp.
The Immune Response (1967)

FROM the early days of immunology, immediate hypersensitivity responses, or the antibody-mediated reactions, were separated from and contrasted with the delayed hypersensitivity response, or the cell-mediated reaction. The reasons for this sharp separation were numerous and cogent. The purpose of this presentation is to point out that the 2 types of reactions have some very important basic similarities. They may both be mediated by antibody, and the observed differences merely reflect the locus of the reaction and the chemical and biologic properties of the antibodies involved. Because an extensive literature has now accumulated in this field, I must be both . . .
Size Dependent Liposome Degradation in Blood:In vivo/In vitroCorrelation by Kinetic Modeling (1995)

The degradation of liposomes in blood circulation is important in regulating the releasing rate of encapsulated compounds. In this study, the effect of liposome size--one of the principal determining factors in liposome disposition--on their degradation in serum/blood was evaluated quantitatively both in vitro and in vivo. In the in vitro study, the time courses of the degradation of liposomes in fresh rat serum were measured continuously using 5(6)-carboxyfluorescein (CF) as an aqueous phase marker and were described by the kinetic model with the lag time (tau), first order degradation rate constant (k), and the maximum degradation (alpha). Both k and alpha increased with the increase of liposome size, which indicated a higher affinity of larger liposomes for complement activation. In the in vivo study, the degradation of liposomes was evaluated sensitively by a first order degradation rate constant (kd) in blood circulation. The kd was obtained by kinetically modeling the liposome degradation in vivo using 3H-inulin as an aqueous phase marker. The size dependent kd correlated well with the hepatic uptake clearance, which suggests an underlying complement activation mechanism common to both degradation and hepatic uptake of liposomes. There was a good correlation in the degradation rate constant between in vitro and in vivo trials. These kinetic analyses validate the quantitative evaluation of liposome degradation in blood circulation and provide a useful way to predict the degradation of liposomes in vivo from in vitro experiments.
Inter-vehicle communication: technical issues on vehicle control application (1996)

Mutual exchange of status data between vehicles in close proximity is the basis for safe vehicle operation. Application areas range from driver assistance/warning to fully autonomous driving. To enable this data exchange we need an intervehicle communication (IVC) system. Vehicles involved in mutual data exchange form a kind of local area network; however, the characteristics of this network are quite different from those of conventional networks. The configuration of this kind of network changes from time to time, in terms of organization, proximity group, group position, and relative position; therefore, it is very challenging to establish. The authors have been working on this problem from the point of view of communication media and protocol. The characteristics and requirements of IVC are discussed, and several preliminary communication protocols are proposed. The authors also present some experimental results from the implementation of a function integrating communication by infrared ray with a gap-measuring technique by the vision system.
X-ray Structure of 5-Aminolevulinic Acid Dehydratase from Escherichia coli Complexed with the Inhibitor Levulinic Acid at 2.0 Å Resolution (1999)

5-Aminolevulinic acid dehydratase (ALAD), an early enzyme of the tetrapyrrole biosynthesis pathway, catalyzes the dimerization of 5-aminolevulinic acid to form the pyrrole, porphobilinogen. ALAD from Escherichia coli is shown to form a homo-octameric structure with 422 symmetry in which each subunit adopts the TIM barrel fold with a 30-residue N-terminal arm. Pairs of monomers associate with their arms wrapped around each other. Four of these dimers interact, principally via their arm regions, to form octamers in which each active site is located on the surface. The active site contains two lysine residues (195 and 247), one of which (Lys 247) forms a Schiff base link with the bound substrate analogue, levulinic acid. Of the two substrate binding sites (referred to as A and P), our analysis defines the residues forming the P-site, which is where the first ALA molecule to associate with the enzyme binds. The carboxyl group of the levulinic acid moiety forms hydrogen bonds with the side chains of Ser 273 and Tyr 312. In proximity to the levulinic acid is a zinc binding site formed by three cysteines (Cys 120, 122, and 130) and a solvent molecule. We infer that the second substrate binding site (or A-site) is located between the triple-cysteine zinc site and the bound levulinic acid moiety. Two invariant arginine residues in a loop covering the active site (Arg 205 and Arg 216) appear to be appropriately placed to bind the carboxylate of the A-site substrate. Another metal binding site, close to the active site flap, in which a putative zinc ion is coordinated by a carboxyl and five solvent molecules may account for the activating properties of magnesium ions.
The Effects of Epinephrine, Norepinephrine, and Phenylephrine on the Types of Proteins Secreted by Rat Salivary Glands (1980)

The types of proteins secreted by rat submandibular glands in response to secretory stimulation with epinephrine, norepinephrine, or phenylephrine were dose-dependent. At relatively high doses the proteins secreted were characteristic of alpha-adrenergic stimulation, whereas at low doses they were characteristic of beta-adrenergic stimulation.
Engineering Yarrowia lipolytica to express secretory invertase with strong FBA1IN promoter (2011)

Oleaginous yeast Yarrowia lipolytica is an important host for the production of lipid-derived compounds or heterologous proteins. Selection of strong promoters and effective expression systems is critical for heterologous protein secretion. To search for a strong promoter in Y. lipolytica, activities of FBA1, TDH1 and GPM1 promoters were compared to that of TEF1 promoter by constructing GUS reporter fusions. The FBA1 promoter activity was 2.2 and 5.5 times stronger than the TDH1 and GPM1 promoters, respectively. The FBA1IN promoter (FBA1 sequence of -826 to +169) containing an intron (+64 to +165) showed five-fold higher expression than the FBA1 promoter (-831 to -1). The transcriptional enhancement by the 5'-region within the FBA1 gene was confirmed by GPM1::FBA1 chimeric promoter construction. Using the strong FBA1IN promoter, four different S. cerevisiae SUC2 expression cassettes were tested for the SUC+ phenotype in Y. lipolytica. Functional invertase secretion was facilitated by the Xpr2 prepro-region with an additional 13 amino acids of mature Xpr2, or by the native Suc2 signal sequence. However, these two secretory signals in tandem, or the mature Suc2 with no secretory signal, did not direct secretion of functional invertase. Unlike previously reported Y. lipolytica SUC+ strains, our engineered stains secreted most of invertase into the medium.
A novel method for studying preadipocyte differentiation in vitro. (1996)

In vitro differentiation of rat preadipocytes has typically been induced in medium supplemented with pharmacological concentrations of hormonal mixtures. These conditions probably do not reflect the milieu within adipose tissue in vivo. We have developed a new method for inducing differentiation of preadipocytes using culture medium which has been conditioned by isolated adipocytes (ACM). In the presence of ACM, 70%-80% of test preadipocytes contained lipid inclusions compared to < 5% of control. When differentiation was assessed by assay of glycerol-3-phosphate dehydrogenase activity, ACM activity was shown to be reproducible and the consistency of response to ACM by different pools of preadipocytes was comparable to that induced by standard differentiation procedures. We have also demonstrated that the adipogenic activity of ACM may not depend on prostaglandin secretion by adipocytes. We propose that use of paracrine factors produced by components of adipose tissue provides a new approach to preadipocyte differentiation induction which may more closely reproduce the adipose tissue environment.
Combined Erlotinib and PF‐03084014 treatment contributes to synthetic lethality in head and neck squamous cell carcinoma (2017)

These results suggested that concomitant inhibition of the Notch1 and EGFR pathways represented a rational strategy for promoting apoptosis in HNSCC and overcoming treatment resistance.
Risks to the public (2012)

column Risks to the public Share on Author: Peter G. Neumann SRI International Computer Science Lab, Menlo Park, CA SRI International Computer Science Lab, Menlo Park, CAView Profile Authors Info & Claims ACM SIGSOFT Software Engineering NotesVolume 37Issue 4July 2012 pp 20–29https://doi.org/10.1145/2237796.2237800Online:16 July 2012Publication History 0citation522DownloadsMetricsTotal Citations0Total Downloads522Last 12 Months2Last 6 weeks0 Get Citation AlertsNew Citation Alert added!This alert has been successfully added and will be sent to:You will be notified whenever a record that you have chosen has been cited.To manage your alert preferences, click on the button below.Manage my AlertsNew Citation Alert!Please log in to your account Save to BinderSave to BinderCreate a New BinderNameCancelCreateExport CitationPublisher SiteGet Access
Presentation and Detection of Azide Functionality in Bacterial Cell Surface Proteins (2004)

An improved protocol for copper-catalyzed triazole formation on the bacterial cell surface is described. Addition of highly pure CuBr to cells treated with azidohomoalanine (2) leads to ca. 10-fold more extensive cell surface labeling than previously observed. This highly active catalyst allows detection of the methionine analogues azidoalanine (1), azidonorvaline (3), and azidonorleucine (4) in cell surface proteins. Azidoalanine was previously believed to be silent with regard to the cellular protein synthesis machinery.
Cell Transplantation in Liver-Directed Gene Therapy (1993)

Somatic cell gene therapy is a new field of biomedical research that encompasses a variety of traditional basic research and clinical disciplines. This new approach to therapeutics has the potential to prevent, treat, or cure a variety of inherited and acquired diseases. Two divergent strategies of hepatocyte transplantation are being employed in animal models and clinical trials in an attempt to correct genetic deficiencies. Allogeneic hepatocyte transplantation has two main advantages over autologous cell transplantation. First, invasive surgical procedures are not required in the recipient. Second, allogeneic cells can be administered repetitively, so that multiple harvests are not necessary. The major drawbacks to allogeneic hepatocyte transplants are rejection and the risks of immunosuppression. Although there is no clinical experience with the treatment of genetic disease by allogeneic hepatocyte transplantation, a variety of animal models have been characterized, including the Gunn rat (UDP-glucuronosyl transferase deficient), the Nagase analbuminemic rat, and the Watanabe heritable hyperlipidemic rabbit (LDL receptor deficient). The use of genetically corrected autologous cells represents a different and more elegant approach to the correction of inherited disease. A segment of liver is harvested from the affected individual. Recombinant retroviruses are used to transduce normal genes--with a variety of promoter/enhancer constructs--into the patients own hepatocytes. The genetically corrected hepatocytes are then transplanted back into the patient. This approach, known as ex vivo gene therapy, eliminates the risk of rejection and the need for immunosuppression. The safety and efficacy of this approach has been proven in a variety of preclinical animals models, including Watanabe rabbits, dogs, and Papio spp. A clinical trial for the treatment of familial hypercholesterolemia is currently in progress. A number of approaches for the reintroduction of hepatocytes into the recipient have been proposed, including catheter-mediated delivery into the inferior mesenteric vein, the umbilical vein, or into the spleen. Candidate diseases, which are likely to result in the first clinical trials include familial hypercholesterolemia, ornithine transcarbamylase deficiency, Crigler-Najjar syndrome, alpha 1-antitrypsin deficiency, and phenylketonuria.
Mercury Methylation by Dissimilatory Iron-Reducing Bacteria (2006)

The Hg-methylating ability of dissimilatory iron-reducing bacteria in the genera Geobacter, Desulfuromonas, and Shewanella was examined. All of the Geobacter and Desulfuromonas strains tested methylated mercury while reducing Fe(III), nitrate, or fumarate. In contrast, none of the Shewanella strains produced methylmercury at higher levels than abiotic controls under similar culture conditions. Geobacter and Desulfuromonas are closely related to known Hg-methylating sulfate-reducing bacteria within the Deltaproteobacteria.
Purification of human anti-TF (Thomsen-Friedenreich) and anti-Tn antibodies by affinity chromatography on glycophorin A derivatives and characterization of the antibodies by microtiter plate ELISA. (1998)

The TF and Tn antigens were obtained from glycophorin A (GPA) by desialylation under mild acidic conditions and by desialylation followed by Smith degradation, respectively. A method of purification of anti-TF and anti-Tn antibodies from human sera by affinity chromatography on the immobilized asialoGPA (TF antigen) and on asialo-agalactoGPA (Tn antigen), respectively, is described. Purity of the antibodies was demonstrated by SDS-polyacrylamide gel electrophoresis and their specific reactivity with TF or Tn antigens was shown using hemagglutination and the microtiter plate ELISA. A high unspecific binding of human immunoglobulins to the ELISA plates was encountered, therefore optimal conditions for the most specific binding of the antibodies to the target antigens were selected. Problems of the unspecific binding of immunoglobulins were more difficult to overcome when the antibodies were determined in whole sera by their binding to antigen-coated ELISA plates.
A new immunosuppressant, FTY720, induces bcl‐2‐associated apoptotic cell death in human lymphocytes (1996)

FTY720 is a unique immunosuppressive drug produced by modification of a metabolite from Isaria sinclairii. In vitro treatment of human mononuclear cells with FTY720 resulted in a dose-dependent reduction of cell viability. These treated cells demonstrated characteristic DNA ladder formation on agarose gel electrophoresis. Jurkat cells transfected with human bcl-2 gene were resistant to FTY720; their neo type was susceptible to the drug. A rapid acceleration of cell death in human mononuclear cells was seen as early as 2 hr after incubation with FTY720. The intracellular Bax protein increased remarkably 1 hr after the culture; it markedly decreased in the surviving cells at 2 and 3 hr. Coincidental to the Bax decrease. Bcl-2 progressively decreased beginning 2 hr after the culture. Thus, the ratio of Bcl-2 to Bax was decreased by the enhanced expression of Bax immediately after FTY720-treatment, resulting in rapid cell death acceleration. The surviving cells (FTY720-resistant cells) at 2 and 3 hr after culture showed a similar ratio of Bcl-2 to Bax as was observed in the control cells. These results suggest that FTY720 displays bcl-2-associated apoptotic cell death in human mononuclear cells.
Fast and SNP-tolerant detection of complex variants and splicing in short reads (2010)

Source code in C and utility programs in Perl are freely available for download as part of the GMAP package at http://share.gene.com/gmap.
Botulinum Toxin Type A as an Effective Prophylactic Treatment in Primary Headache Disorders (2003)

These results suggest that botulinum toxin type A may be an effective and safe prophylactic treatment for a variety of moderate to severe chronic headache types.
Glucose Is Necessary for Embryonic Pancreatic Endocrine Cell Differentiation (2007)

Mature pancreatic cells develop during embryonic life from endodermal progenitors, and this developmental process depends on activation of a hierarchy of transcription factors. While information is available on mesodermal signals controlling pancreas development, little is known about environmental factors, such as the levels of nutrients including glucose, that may control this process. Here, we studied the effects of glucose on pancreatic cells development. We used an in vitro model where both endocrine and acinar cells develop from early pancreatic and duodenal homeobox-1 (PDX1)-positive embryonic pancreatic progenitors. We first showed that glucose does not have a major effect on global pancreatic cell proliferation, survival, and acinar cell development. On the other hand, glucose controlled both alpha and beta cell development. Specifically, the surface occupied by insulin-positive cells was 20-fold higher in pancreases cultured in presence than in absence of glucose, and this effect was dose-dependent over the range 0.5-10 mm. Glucose did not appear to control beta cell development by activating the proliferation of early progenitors or beta cells themselves but instead tightly regulated cell differentiation. Thus, glucose did not modify the pattern of expression of Neurogenin3, the earliest marker of endocrine progenitor cells, but was necessary for the expression of the transcription factor NeuroD, a direct target of Neurogenin3 known to be important for proper pancreatic endocrine cell development. We conclude that glucose interferes with the pancreatic endocrine cells development by regulating the transition between Ngn3 and upstream NeuroD.
Four-channel optically pumped atomic magnetometer for magnetoencephalography (2016)

We have developed a four-channel optically pumped atomic magnetometer for magnetoencephalography (MEG) that incorporates a passive diffractive optical element (DOE). The DOE allows us to achieve a long, 18-mm gradiometer baseline in a compact footprint on the head. Using gradiometry, the sensitivities of the channels are < 5 fT/Hz<sup>1/2</sup>, and the 3-dB bandwidths are approximately 90 Hz, which are both sufficient to perform MEG. Additionally, the channels are highly uniform, which offers the possibility of employing standard MEG post-processing techniques. This module will serve as a building block of an array for magnetic source localization.