gebhart/patrepeval huggingface dataset:
Bispecific anti-idiotype/anti-CD3 antibody therapy of murine B cell lymphoma (1991)

Abstract Retargeting of T cells by bispecific IgG which binds to both CD3 and a tumor-associated Ag can induce T cell lysis of target cells irrespective of TCR specificity. The current studies were designed to further explore the efficacy and specificity of bispecific IgG-directed therapy in an immunocompetent animal model, and to evaluate the mechanisms responsible for bispecific IgG-directed inhibition of tumor cell growth by using the 38C13 murine lymphoma system. In vitro, proliferation of activated T cells in the presence of bispecific IgG was increased when the relevant, but not the irrelevant target cells were present. Bispecific IgG specifically induced activated T cell mediated lysis of cells expressing the target Ag, but not of cells expressing an irrelevant Ag, even when the irrelevant cells were in the same cell mixture, indicating contact between target cells and T cells plays a major role in bispecific IgG-mediated lysis. Bispecific IgG was less effective than anti-Id at inducing target cell lysis when peritoneal macrophages were used as effectors, suggesting bispecific IgG Fc is not responsible for cytotoxicity in this system. In vivo, bispecific IgG was significantly superior to anti-Id, anti-CD3, or a combination of anti-Id and anti-CD3 in preventing tumor growth in immunocompetent mice inoculated with syngeneic lymphoma. Phenotypic evaluation of tumors that emerged despite therapy indicated bispecific IgG selects for the emergence of Id variant lymphoma cells. In separate studies, 38C13 tumor inocula containing cells recognized by the therapeutic antibody were supplemented with a small number of 38C13 cells which expressed a distinct Id not recognized by the therapeutic antibody. Untreated mice inoculated with this mixture developed tumors containing cells of both phenotypes, whereas tumors emerging from mice treated with bispecific IgG contained only cells expressing the nonreactive Id. These studies demonstrate bispecific IgG-directed lysis is therapeutically superior to monospecific anti-Id therapy in the 38C13 tumor model, and that tumor lysis is mediated largely by cell-cell contact. As with other forms of anti-Id based therapy, Id variants can emerge as resistant cell populations after bispecific IgG therapy.
Hypomyelinating peripheral neuropathies and schwannomas in transgenic mice expressing SV40 T-antigen (1994)

We have prepared transgenic mice carrying a temperature-sensitive mutant of the SV40 oncogene (tsA-1609) under the control of 5' flanking sequences from the Schwann cell-specific P0 gene. Four of six founder mice showed moderate to severe hypomyelination in peripheral nerves of tail biopsies, with only rare myelinated fibers. Offspring were obtained from three of these founders. Northern blot and immunohistochemical analyses showed that expression of T-antigen was restricted to the PNS. Mice expressing the highest levels of T-antigen exhibited the most severe hypomyelination. Mice expressing lower levels developed transient mild hypomyelination, but after long latencies developed sporadic schwannomas. An immortalized cell line exhibiting properties of Schwann cells at an arrested stage of differentiation, termed "SCT-1," was derived from one of these tumors.
Candidate genes for recessive non‐syndromic mental retardation on chromosome 3p (MRT2A)* (2004)

A mild type of autosomal recessive, non-syndromic mental retardation (NSMR) is linked to loci on chromosome 3p. This report delimits the MRT2A minimal critical region to 4.2 Mb between loci D3S3630 and D3S1304. This interval contains nine genes (IL5RA, TRNT1, LRRN1, SETMAR, SUMF1, ITPR1, BHLHB2, EDEM, and MRPS36P1). The results suggest that a mutation does not exist in these genes and that an unknown transcript in the region contributes to the cognitive deficits in NSMR.
Interferon in AIDS. (1987)

Interferons are natural proteins with important regulatory functions. Impairment of their production may help to explain many of the immunologic abnormalities and disease susceptibilities of AIDS patients, while excessive production of an unusual type of interferon may explain some of the systemic symptoms associated with the syndrome. In a subset of patients, alpha interferons may have therapeutic potential against a major complication of the syndrome, Kaposi's sarcoma. Finally, both alpha and gamma interferons have potential, but as yet unexplored roles to play in the treatment of HTLV-III/LAV viremia and in the control of secondary infectious complications of the syndrome.
Lymphocyte apoptosis in acute respiratory syncytial virus bronchiolitis (2004)

Respiratory syncytial virus (RSV) infection may have an effect on the development of T cell memory responses. RSV bronchiolitis in infants is associated with a transient decline in circulating lymphocytes. We hypothesized that the mechanism underlying this lymphopenia is apoptosis. Blood was taken from 32 infants during primary RSV bronchiolitis and three months later. Using flow cytometry, we found that absolute numbers of both CD3+/CD4+ T-helper lymphocytes (P = 0.029) and CD3+/CD8+ cytotoxic lymphocytes (CTL) (P = 0.043) were significantly reduced during acute infection. Up-regulated expression both of Fas (P < 0.001) and tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor (P < 0.001) was found during acute illness on both CD3+/CD4+ and CD3+/CD8+ lymphocytes, when compared with convalescent samples. Expression of Fas on CD4+ lymphocytes was inversely related to CD4+ number (P = 0.03). Plasma levels of soluble Fas ligand (P = 0.028) and caspase-1 (P = 0.037), determined by enzyme-linked immunosorbent assay, were increased during bronchiolitis. Plasma interleukin-18, a product of caspase-1 activity, was not raised. Taken together, these data suggest that in acute RSV infection, CD4+ helper lymphocytes and CD8+ cytotoxic lymphocytes are primed to undergo apoptosis. This is a mechanism through which lymphopenia may occur and T cell memory may be altered.
Space-time modems for wireless personal communications (1998)

This article reviews space-time modem technology for mobile radio applications. We begin with motivations for the use of space-time modems and then briefly discuss the challenges posed by wireless propagation. Next, we develop a signal model for the wireless environment. Channel estimation, equalization, and filtering techniques for space-time modems in the forward and reverse links are then discussed. Finally, we review applications of space-time modems to cellular systems and discuss industry trends.
Maximum matching and a polyhedron with 0,1-vertices (1965)

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Tinkering with meiosis (2012)

Meiosis is at the heart of Mendelian heredity. Recently, much progress has been made in the understanding of this process, in various organisms. In the last 15 years, the functional characterization of numerous genes involved in meiosis has dramatically deepened our knowledge of key events, including recombination, the cell cycle, and chromosome distribution. Through a constantly advancing tool set and knowledge base, a number of advances have been made that will allow manipulation of meiosis from a plant breeding perspective. This review focuses on the aspects of meiosis that can be tinkered with to create and propagate new varieties. We would like to dedicate this review to the memory of Simon W. Chan (1974-2012) (http://www.plb.ucdavis.edu/labs/srchan/).
Optimal Path Planning for Robotic Insertion of Steerable Electrode Arrays in Cochlear Implant Surgery (2008)

This paper presents an optimal path planning method of steerable electrode arrays for robot-assisted cochlear implant surgery. In this paper, the authors present a novel design of steerable electrode arrays that can actively bend at the tip. An embedded strand in the electrode array provides an active steering degrees-of-freedom (DoF). This paper addresses the calibration of the steerable electrode array and the optimal path planning for inserting it into planar and three-dimensional scala tympani models. The goal of the path planning is to minimize the intracochlear forces that the electrode array applies on the walls of the scala tympani during insertion. This problem is solved by designing insertion path planning algorithms that provide best fit between the shape of the electrode array and the curved scala tympani during insertion. Optimality measures that account for shape discrepancies between the steerable electrode array and the scala tympani are used to solve for the optimal path planning of the robot. Different arrangements of DoF and insertion speed force feedback (ISFF) are simulated and experimentally validated in this paper. A quality of insertion metric describing the gap between the steerable electrode array and the scala tympani model is presented and its correspondence to the insertion force is shown. The results of using 1DoF, 2DoF, and 4DoF electrode array insertion setups are compared. The 1DoF insertion setup uses nonsteerable electrode arrays. The 2DoF insertion setup uses single axis insertion with steerable electrode arrays. The 4DoF insertion setup allows full control of the insertion depth and the approach angle of the electrode with respect to the cochlea while using steerable electrode arrays. It is shown that using steerable electrode arrays significantly reduces the maximal insertion force (59.6% or more) and effectively prevents buckling of the electrode array. The 4DoF insertion setup further reduces the maximal electrode insertion forces. The results of using ISFF for steerable electrodes show a slight decrease in the insertion forces in contrast to a slight increase for nonsteerable electrodes. These results show that further research is required in order to determine the optimal ISFF control law and its effectiveness in reducing electrode insertion forces.
Combined effect of chelating agents and ultrasound on biofilm removal from stainless steel surfaces. Application to “Escherichia coli milk” and “Staphylococcus aureus milk” biofilms (2004)

Two ultrasonic devices – flat (T1) and curved (T2) ultrasonic transducers – were developed to remove biofilms from opened and closed surfaces, respectively. The aim is to standardize biofilm removal for in situ sanitary control in the food industry. The biofilms studied in this work were model biofilms made with milk on stainless steel sheets. We have shown in a previous study that sonication could be employed to remove and resuspend biofilm consistently, with a good recovery rate, from opened surfaces. Plate counting was used to assess the efficiency of each treatment. A total removal of Escherichia coli and Staphylococcus aureus from model biofilms was obtained with T1: 10 s at 40 kHz. However, ultrasound applied with T2 (a patented curved transducer developed for closed surfaces: 10 s at 40 kHz) failed to completely remove these model biofilms: 30±7% and 66±10% for E. coli and S. aureus biofilms, respectively. In order to improve the biofilm removal from closed surfaces with T2, the effect of the application of ultrasound in combination with chelating agent preparations was investigated. The application of ultrasound with T2 in 0.05 mol EDTA or EGTA per litre dislodged the E. coli milk model biofilm, with 100±10% and 100±5% recovery yields, respectively. These results showed a synergism between ultrasonic waves and chelator preparations, i.e. the combination achieved three times the recovery rate of sonication alone (30%). However, when the same treatment was applied to the S. aureus milk model biofilm, the combined treatment with EDTA or EGTA did not significantly improve the recovery of the biofilm cells: 74±26% with EDTA at 0.025 mol/l and 41–47% with EGTA at 0.025 mol/l and 0.05 mol/l, respectively, compared with 66±10% for sonication alone. The combined treatment was in agreement with an industrial control, i.e. a good reproducible recovery of the biofilm in a few seconds (10 s) for E. coli milk biofilms but not for S. aureus biofilms.
Pseudomonas aeruginosa Uses Multiple Pathways To Acquire Iron during Chronic Infection in Cystic Fibrosis Lungs (2013)

Pseudomonas aeruginosa chronically infects the lungs of more than 80% of adult patients with cystic fibrosis (CF) and is a major contributor to the progression of disease pathology. P. aeruginosa requires iron for growth and has multiple iron uptake systems that have been studied in bacteria grown in laboratory culture. The purpose of this research was to determine which of these are active during infection in CF. RNA was extracted from 149 sputum samples obtained from 23 CF patients. Reverse transcription-quantitative real-time PCR (RT-qPCR) was used to measure the expression of P. aeruginosa genes encoding transport systems for the siderophores pyoverdine and pyochelin, for heme, and for ferrous ions. Expression of P. aeruginosa genes could be quantified in 89% of the sputum samples. Expression of genes associated with siderophore-mediated iron uptake was detected in most samples but was at low levels in some samples, indicating that other iron uptake mechanisms are active. Expression of genes encoding heme transport systems was also detected in most samples, indicating that heme uptake occurs during infection in CF. feoB expression was detected in all sputum samples, implying an important role for ferrous ion uptake by P. aeruginosa in CF. Our data show that multiple P. aeruginosa iron uptake mechanisms are active in chronic CF infection and that RT-qPCR of RNA extracted from sputum provides a powerful tool for investigating bacterial physiology during infection in CF.
Molecular architectures of multi-anthracene assemblies (2013)

Anthracene, with its molecular panel-like shape and robust photophysical behaviour, is a versatile building block that is widely used to construct attractive and functional molecules and molecular assemblies through covalent and non-covalent linkages. The intrinsic photophysical, photochemical and chemical properties of the embedded anthracenes often interact to engender desirable chemical behaviours and properties in multi-anthracene assemblies. This review article focuses on molecular architectures with linear, cyclic, cage, and capsule shapes, each containing three or more anthracene subunits.
A Convenient Method for the Preparation of 1‐(tert‐Butyloxycarbonyl) pyrroles (1984)

Attachment of the Boc group to pyrrole nitrogen can now be achieved by a universally applicable method. Preparation of the N-Boc derivatives 1 from the corresponding pyrroles has been accomplished with Boc2O in presence of the strong acylating catalyst 4-dimethylaminopyridine in CH3CN or CH2Cl2 at room temperature. A wide variety of substituents R1—R4 can be used.
Cloning and expression of the essential gene for guanylate kinase from yeast. (1992)

Guanylate kinase catalyzes the reversible transfer of the terminal phosphoryl group of ATP to the acceptor molecule GMP. Detailed analysis of the in vivo function of this enzyme has been limited by the lack of any genetic data. Using oligonucleotides based on amino acid sequence information of the yeast enzyme, the Saccharomyces cerevisiae gene, GUK1, was isolated and characterized. The gene is present in single copy and maps to chromosome IV. Insertional mutagenesis of the GUK1 locus caused recessive lethality, indicating that this enzyme is necessary for vegetative cell growth. Using inducible expression systems, guanylate kinase was produced in large amounts both in S. cerevisiae and in Escherichia coli.
Modification of fibrin to improve applications in regenerative medicine (2009)

Die Methode von Tissue Engineering oder der Gewebezuchtung drangt uns Matrizen oder Stutzgeruste , die Gewebearten imitieren in vitro zu entwickeln. Tissue Engineering setzt die Prasenz von sich regenerierenden Zellen, biologisch degradierenden Matrizen und Bioreaktoren, die die zellulare Umwelt regulieren. Zellen und biologische Matrizen konnen mit unterschiedlichen Methoden verwendet werden.
Fibrin stellt eine gut anwendbare biologisch abbaubare Matrix, an die regulatorische Faktoren wie Wachstumsfaktoren binden, dar. In unseren Studien testeten wir Fibroblasten Wachstumsfaktor 2 (FGF-2) Peptide, welche eine Bindungsaffinitat zu Fibrin(ogen) aufweisen, auf ihre biologische Aktivitat an isolierten humanen Fettstammzellen. FGF-2 Peptide hatten keine Auswirkung auf die Proliferation der Zellen, aber fuhrten zu einer Erhohung der Kollagen Ia2 und Kollagen III mRNA Expression innerhalb einer Inkubationszeit von 7 Tagen. Weitere Experimente beschaftigten sich mit dem kontrollierten Freisetzung von Substanzen aus Fibrin. Substanzen, die keine naturliche Bindungsaffinitat zu Fibrin(ogen) aufweisen, wurden an sogenannte Fibrin-Anker (Fibronektin oder Trombin), die eine Bindedomane zu Fibrin(ogen) haben, gebunden. Mit diesem System zeigte sich eine kontinuierliche Freisetzung dieser Substanzen aus der Fibrinmatrix.
Eine weiter Methode der Modifikation von Fibrin war die Produktion von Fibrinmatten durch elektrisches Spinnen. Fibrinogen und Trombin wurden in einer Hexafluoroisopropanol-Losung gelost und zu Nanofasern gesponnen. Auf Grund des geringen Durchmessers der Nanofasern bilden sie eine attraktive Matrix fur Zellkontakte. Die Ahnlichkeit in der Grose des Netzwerks und der 3-dimensionalen Anordnung der Nanofasern zu extrazellularen Matrixcomponenten erleichtern Zellen den Kontakt und die Anhaftung zur Matrix.
Zuletzt beschaftigten wir uns noch mit einer neuen Methode um 3-dimensionale mesenchymale Stammzell-Konstrukte in Fibrin zu erzeugen. Amniotische mesenchymale Stammzellen wurden mit Fibrin vermischt. Innerhalb von 8 Tagen wurde das Fibrin durch die zellulare Spannung zu einem schlauchartigen Konstrukt kontrahiert. Dieses Fibrin-Zell-Konstrukt wurde in einem Bioreaktor uber einen Zeitraum von 14 Tagen mit 0.1 Hz auf eine Lange von 114% gedehnt. Histologische Untersuchungen zeigten eine hohe Dichte von Kollagen im gedehnten Bereich. Diese Resultate weisen auf eine neue Methode zur Produktion in vitro von funktionellen Konstrukten wie Sehnen oder Bander hin.
Dextran Sulphate 500 Delays and Prevents Mouse Scrapie by Impairment of Agent Replication in Spleen (1984)

SUMMARY Treatment of scrapie-infected mice with dextran sulphate (DS) 500 resulted in considerably reduced spleen titres over a long period of time. Subsequently, the central nervous system disease was delayed or even prevented during the 350-day period of observation. Both effects increased after multiple injections of the compound. The potency of DS 500 to protect against scrapie was greatest when treatment and infection were carried out simultaneously. Under these conditions the lethality of 500 to 1000 LD50 was reduced to almost zero. Treatment as early as 10 weeks before infection still prolonged the incubation periods. Of several other polyions tested, dextran sulphate 5 and pentosan polysulphate also impaired scrapie pathogenesis.
ATP Release From Activated Neutrophils Occurs via Connexin 43 and Modulates Adenosine-Dependent Endothelial Cell Function (2006)

Extracellular ATP liberated during hypoxia and inflammation can either signal directly on purinergic receptors or can activate adenosine receptors following phosphohydrolysis to adenosine. Given the association of polymorphonuclear leukocytes (PMNs) with adenine-nucleotide/nucleoside signaling in the inflammatory milieu, we hypothesized that PMNs are a source of extracellular ATP. Initial studies using high-performance liquid chromatography and luminometric ATP detection assays revealed that PMNs release ATP through activation-dependent pathways. In vitro models of endothelial barrier function and neutrophil/endothelial adhesion indicated that PMN-derived ATP signals through endothelial adenosine receptors, thereby promoting endothelial barrier function and attenuating PMN/endothelial adhesion. Metabolism of extracellular ATP to adenosine required PMNs, and studies addressing these metabolic steps revealed that PMN express surface ecto-apyrase (CD39). In fact, studies with PMNs derived from cd39(-/-) mice showed significantly increased levels of extracellular ATP and lack of ATP dissipation from their supernatants. After excluding lytic ATP release, we used pharmacological strategies to reveal a potential mechanism involved in PMN-dependent ATP release (eg, verapamil, dipyridamole, brefeldin A, 18-alpha-glycyrrhetinic acid, connexin-mimetic peptides). These studies showed that PMN ATP release occurs through connexin 43 (Cx43) hemichannels in a protein/phosphatase-A-dependent manner. Findings in human PMNs were confirmed in PMNs derived from induced Cx43(-/-) mice, whereby activated PMNs release less than 15% of ATP relative to littermate controls, whereas Cx43 heterozygote PMNs were intermediate in their capacity for ATP release (P<0.01). Taken together, our results identify a previously unappreciated role for Cx43 in activated PMN ATP release, therein contributing to the innate metabolic control of the inflammatory milieu.
Role of methionine and formylation of initiator tRNA in initiation of protein synthesis in Escherichia coli (1992)

We showed recently that a mutant of Escherichia coli initiator tRNA with a CAU-->CUA anticodon sequence change can initiate protein synthesis from UAG by using formylglutamine instead of formylmethionine. We further showed that coupling of the anticodon sequence change to mutations in the acceptor stem that reduced Vmax/Km(app) in formylation of the tRNAs in vitro significantly reduced their activity in initiation in vivo. In this work, we have screened an E. coli genomic DNA library in a multicopy vector carrying one of the mutant tRNA genes and have found that the gene for E. coli methionyl-tRNA synthetase (MetRS) rescues, partially, the initiation defect of the mutant tRNA. For other mutant tRNAs, we have examined the effect of overproduction of MetRS on their activities in initiation and their aminoacylation and formylation in vivo. Some but not all of the tRNA mutants can be rescued. Those that cannot be rescued are extremely poor substrates for MetRS or the formylating enzyme. Overproduction of MetRS also significantly increases the initiation activity of a tRNA mutant which can otherwise be aminoacylated with glutamine and fully formylated in vivo. We interpret these results as follows. (i) Mutant initiator tRNAs that are poor substrates for MetRS are aminoacylated in part with methionine when MetRS is overproduced. (ii) Mutant tRNAs aminoacylated with methionine are better substrates for the formylating enzyme in vivo than mutant tRNAs aminoacylated with glutamine. (iii) Mutant tRNAs carrying formylmethionine are significantly more active in initiation than those carrying formylglutamine. Consequently, a subset of mutant tRNAs which are defective in formylation and therefore inactive in initiation when they are aminoacylated with glutamine become partially active when MetRS is overproduced.