gebhart/patrepeval huggingface dataset:
An Immunotoxin Composed of Monoclonal Anti-Thy 1.1 Antibody and a Ribosome-Inactivating Protein From <italic>Saponaria officinalis:</italic> Potent Antitumor Effects In Vitro and In Vivo (1985)

The ribosome-inactivating protein saporin, from Saponaria officinalis, was coupled by a disulfide bond to monoclonal anti-Thy 1.1 antibody (OX7) and to its F(ab')2 fragment. The immunotoxins were at least as toxic as the plant toxin ricin to the Thy 1.1-expressing cell lines AKR-A and BW5147 in tissue culture. They reduced the rate at which the cells incorporated [3H]leucine into protein by 50% at cell concentrations of 1.5-3 X 10(-11) and 3 X 10(-12) M, respectively. The toxic effect was specific. No toxicity was seen when the immunotoxins were applied to Thy 1.2-expressing EL 4 lymphoma cells at 3 X 10(-8) M, and a control immunotoxin made from an antibody (R10) of irrelevant specificity was without effect on AKA-A cells. Further, the treatment of spleen cells from AKR mice with OX7-saporin at 10(-8) M abolished their response to the T-lymphocyte mitogen concanavalin A, without impairing their response to the B-lymphocyte mitogen lipopolysaccharide. A single iv injection of OX7-saporin into nu/nu randombred mice bearing peritoneal AKR-A lymphoma cells prolonged the survival time of the animals by an extent corresponding to that expected if 99.999% of the tumor cells had been eradicated by the immunotoxin. None of the control materials (unconjugated OX7, unconjugated saporin, OX7 plus saporin, or R10-saporin) delayed tumor growth. The OX7 F(ab')2-saporin conjugate was also highly effective as an antitumor agent, although significantly less so than the conjugate made with intact OX7. Unexpectedly, the acute toxicity of saporin to mice (median lethal dose = 6.8 mg/kg) was elevated eightfold to sixteenfold by conjugation to OX7, R10, or OX7 F(ab')2. Histologic examination of recipients of the immunotoxin revealed gross damage to hepatic parenchymal cells and to the white pulp of the spleen, neither of which was caused by unconjugated saporin. Ricin A-chain coupled to OX7 antibody was one hundredfold to one thousandfold less effective than OX7-saporin as an antitumor agent in vivo, although the two immunotoxins were equally cytotoxic to AKR-A cells in vitro.
Noninvasive lung cancer detection via pulmonary protease profiling (2018)

Abstract Lung cancer is the leading cause of cancer-related death and patients most commonly present with incurable metastatic disease. National guidelines recommend screening for high-risk patients with low-dose computed tomography (LDCT), but this approach has limitations including high false positive rates. Activity-based nanosensors (ABNs) detect dysregulated proteases in vivo and release a reporter to provide a urinary readout of disease activity. Here, we demonstrate the translational potential of ABNs by coupling ABN multiplexing with intrapulmonary delivery to detect early-stage lung cancer in an immunocompetent, genetically engineered mouse model (GEMM). The design of the multiplexed panel of sensors was informed by comparative transcriptomic analysis of human and mouse lung adenocarcinoma data sets and in vitro cleavage assays with recombinant candidate proteases. When employed in a Kras and Trp53 mutant lung adenocarcinoma mouse model, this approach confirmed the role of metalloproteases in lung cancer and enabled accurate early detection of disease, with 92% sensitivity and 100% specificity.
The directed modification of Escherichia coli MG1655 to obtain histidine-producing mutants (2013)

Strain MG1655+ hisG r hisL′-ΔΔ, purR, which produces histidine with a weight yield of approximately 12% from glucose, was constructed through directed chromosomal modifications of the laboratory Escherichia coli strain MG1655+, which has a known genome sequence. A feedback-resistant ATP-phosphoribosyl transferase encoded by the mutant hisG r (E271K) was the main determinant of histidine production. A further increase in histidine production was achieved by the expression enhance of a mutant his operon containing hisG r through the deleting attenuator region (hisL′-Δ). An increase in the expression of the wildtype his operon did not result in histidine accumulation. Deletion of the transcriptional regulator gene purR increased the biomass produced and maintained the level of histidine production per cell under the fermentation conditions used.
Improving Real-time Performance of Intelligent Systems with Dynamic Trade-off Evaluation (1993)

This paper describes dynamic trade-off evalation (DTE), a new technique that has been developed to improve the performance of real-time problem solving systems. The DTE technique is most suitable for environments in which the requirement for meeting time constraints is of equal or greater importance to that of providing optimally intelligent solutions.
Hyperinducible expression of the interferon-gamma (IFN-γ) gene and its suppression in systemic lupus erythematosus (SLE) (1997)

Transient expression of IFN-gamma and IL-2 mRNA and its control by post-transcriptional and suppressive mechanisms were analysed in phytohaemagglutinin-induced peripheral blood mononuclear cells (PBMC) from 47 patients with SLE and 31 age-matched normal donors, using quantitative hybridization with antisense RNA probes. In SLE, basal levels of gene expression did not deviate from those of normal donors, but strongly aberrant patterns were obtained upon induction. The ratio of subjects exhibiting highly inducible IFN-gamma gene expression in their PBMC to those showing moderate or low inducibility was increased five-fold in SLE (P = 0.003). High inducibility was observed for 43% of SLE patients and was equally pronounced in partial remission, mild or active disease. Inducibility of IL-2 mRNA, by contrast, remained similar to that for normal donors. However, regulation of IFN-gamma gene expression differed for mild SLE. Patients with mild disease showing high inducibility of IFN-gamma mRNA in their PBMC not only had the highest frequency of responders, but also the highest extent of an individual response, defined by superinduction of mRNA, to agents that relieve suppression (gamma-irradiation) or post-transcriptional down-regulation (cycloheximide). By contrast, patients with active SLE showing high IFN-gamma mRNA inducibility had normal suppressive capacity as well as post-transcriptional control. Hence, both high inducibility of the IFN-gamma gene and its suppression are relevant to disease. Hyperactivation of the IFN-gamma gene may be alleviated in mild SLE by a vigorous, concomitant activation of post-transcriptional control and of cell-mediated suppression.
DNA as a universal substrate for chemical kinetics (2010)

Molecular programming aims to systematically engineer molecular and chemical systems of autonomous function and ever-increasing complexity. A key goal is to develop embedded control circuitry within a chemical system to direct molecular events. Here we show that systems of DNA molecules can be constructed that closely approximate the dynamic behavior of arbitrary systems of coupled chemical reactions. By using strand displacement reactions as a primitive, we construct reaction cascades with effectively unimolecular and bimolecular kinetics. Our construction allows individual reactions to be coupled in arbitrary ways such that reactants can participate in multiple reactions simultaneously, reproducing the desired dynamical properties. Thus arbitrary systems of chemical equations can be compiled into real chemical systems. We illustrate our method on the Lotka-Volterra oscillator, a limit-cycle oscillator, a chaotic system, and systems implementing feedback digital logic and algorithmic behavior.
Cobalt Catalyzed Functionalization of Unactivated Alkenes: Regioselective Reductive C−C Bond Forming Reactions (2009)

The cobalt catalyzed hydroaldoximation and hydrocyanooximation of unactivated alkenes is reported. Secondary and tertiary aldoximes and oximonitriles are synthesized with excellent regioselectivity under mild conditions, and conversion of the products to valuable intermediates is documented. The reactions expand the arsenal of reductive carbon-carbon bond forming reactions as well as regioselective functionalizations of unactivated double bonds.
Monoclonal Antibodies with Affinity to Self-Complementary Left-Handed DNA Containing Cyclonucleosides with High Anti Conformation (1994)

Abstract Monoclonal antibodies specific for a self-complementary hexanucleotide with a high-anti conformation were found to bind another hexanucleotide with a high-anti conformation, but with a different sequence. A higher order structure seemed to be recognized in the reaction.
Selective RGD-Mediated Adhesion of Osteoblasts at Surfaces of Implants (1999)

Osteoblasts: yes, platelets: no! Bone implants have to be integrated with the surrounding tissue to allow a smooth and stable connection. A new procedure is shown which is based on covalent linking of a highly selective RGD peptide to a poly(methyl methacrylate) (PMMA) material (see picture). Osteoblasts very effectively bind to the treated surface and are stimulated to proliferate.
Growth of influenza A virus in primary, differentiated epithelial cells derived from adenoids (1996)

Epithelial cells of adenoid origin were grown in tissue culture to examine viral replication in cells that are the primary target of many human pathogens. These cells remained highly differentiated, with subpopulations of cells which retained active ciliary motility and others which demonstrated specialized secretory functions. The epithelial cells were permissive for growth of influenza A virus. Primary respiratory epithelial cells provide a model system for examining virulence, cell tropism, and receptors which replicate in the nasopharynx.
Resistance to <I>Varroa destructor</I> (Mesostigmata: Varroidae) When Mite-Resistant Queen Honey Bees (Hymenoptera: Apidae) Were Free-Mated with Unselected Drones (2001)

This study demonstrated (1) that honey bees, Apis mellifera L, can express a high level of resistance to Varroa destructor Anderson & Trueman when bees were selected for only one resistant trait (suppression of mite reproduction); and (2) that a significant level of mite-resistance was retained when these queens were free-mated with unselected drones. The test compared the growth of mite populations in colonies of bees that each received one of the following queens: (1) resistant--queens selected for suppression of mite reproduction and artificially inseminated in Baton Rouge with drones from similarly selected stocks; (2) resistant x control--resistant queens, as above, produced and free-mated to unselected drones by one of four commercial queen producers; and (3) control--commercial queens chosen by the same four queen producers and free-mated as above. All colonies started the test with approximately 0.9 kg of bees that were naturally infested with approximately 650 mites. Colonies with resistant x control queens ended the 115-d test period with significantly fewer mites than did colonies with control queens. This suggests that beekeepers can derive immediate benefit from mite-resistant queens that have been free-mated to unselected drones. Moreover, the production and distribution of these free-mated queens from many commercial sources may be an effective way to insert beneficial genes into our commercial population of honey bees without losing the genetic diversity and the useful beekeeping characteristics of this population.
Studies of High Doses of a Human Immunodeficiency Virus Type 1 Recombinant Glycoprotein 160 Candidate Vaccine in HIV Type 1-Seronegative Humans (1994)

We examined the safety and immunogenicity of a baculovirus-derived recombinant HIV-1 envelope glycoprotein vaccine candidate, rgp160 (VaxSyn; MicroGeneSys, Meriden, CT), administered at doses of 160 or 640 micrograms to 56 healthy, HIV-1-seronegative adults, in a randomized, double-blind, placebo-controlled study. Immunizations were given intramuscularly at 0, 1, 6, and 12 months. Both doses were generally well tolerated, although self-limited local reactions were frequent. No other clinical or laboratory toxicities were noted, and no effects on CD4 or CD8 lymphocyte counts or percentages were noted. Serum antibody responses to HIV proteins were detected by Western blot (WB) in 19 of 20 and in 19 of 19 recipients of four doses of 160 and 640 micrograms, respectively. Western blot responses developed more rapidly in the 640-micrograms group. High rates of EIA antibody responses to HIV-1 lysate were also present in both groups, and developed more rapidly in the 640-micrograms group. Enzyme immunoassay antibody responses to the immunogen (rgp160) were also frequent, but were infrequent to V3 to gp41 peptides. Neutralizing antibodies against the homologous HIV-1 LAI isolate were seen in 3 of 20 subjects (GMT = 11) who received four doses of 160 micrograms, and in 10 of 19 subjects who received four doses of 640 micrograms (GMT = 32). Fusion inhibiting antibody was not detected. CD4 blocking activity was seen in 3 of 19 subjects who received four doses of 640 micrograms. Complement-mediated antibody-dependent enhancement was found in sera from 11 of 19 volunteers in the 640-micrograms group. Lymphocyte proliferative responses to the immunogen were detected in 4 of 4 subjects tested, but no cytotoxic T cell activity was noted in 11 subjects. Administration of the 640-micrograms dose of this rgp160 vaccine candidate relative to the lower doses was associated with increased immunogenicity, including higher rates of homologous neutralizing antibody responses, although at low titer.
Compact, 17W average power, 100kW peak power, nanosecond fiber laser system (2013)

We demonstrate a robust, compact, low-cost, pulsed, linearly polarized, 1064 nm, Yb:fiber laser system capable of generating ~100 kW peak power pulses and >17 W average power at repetition rates of 80 – 285 kHz. The system employs a configurable microchip seed laser that provides nanosecond (~1.0 – 1.5 ns) pulse durations. The seed pulses are amplified in an all-fiber, polarization maintaining, large mode area (LMA) fiber amplifier optimized for high peak power operation. The LMA Yb:fiber amplifier enables near diffraction limited beam quality at 100 kW peak power. The seed laser, fiber amplifier, and beam delivery optics are packaged into an air-cooled laser head of 152×330×87 mm3 with pump power provided from a separate air-cooled laser controller. Due to the high peak power, high beam quality, spectral purity, and linearly polarized nature of the output beam, the laser is readily frequency doubled to 532 nm. Average 532 nm powers up to 7 W and peak powers exceeding 40 kW have been demonstrated. Potential for scaling to higher peak and average powers in both the green and infrared (IR) will be discussed. This laser system has been field tested and demonstrated in numerous materials processing applications in both the IR and green, including scribing and marking. We discuss recent results that demonstrate success in processing a diverse array of representative industrial samples.
How silicosis and coal workers' pneumoconiosis develop--a cellular assessment. (1993)

In vitro and in vivo animal studies, as well as human investigations, strongly support the role of macrophage products in the development and progression of silicosis and coal workers' pneumoconiosis. Such products include enzymes and reactive oxygen species which may cause lung damage; cytokines which recruit and/or activate polymorphonuclear leukocytes and thus result in further oxidant damage to the lung; and fibrogenic factors which induce fibroblast proliferation and collagen synthesis. This mechanistic understanding of pulmonary disease should assist in developing strategies for prevention and treatment.
Cdk4 and p27Kip1 play a role in PLC-gamma1-mediated mitogenic signaling pathway of 18 kDa FGF-2 in corneal endothelial cells. (2002)

These data indicate that PLC-gamma1 ultimately leads to activation of the cell cycle machinery to induce cell proliferation mediated by FGF-2. It does so by upregulating Cdk4 expression and by facilitating the nuclear import of the molecule and nuclear export of the Cdk inhibitor (p27-Kip1) to the proteolysis site, the cytoplasm.
Perceptual Audio Coding Using a Time-Varying Linear Pre- and Post-Filter (2001)

LCAV
Recombinant Listeria Vaccines Containing PEST Sequences Are Potent Immune Adjuvants for the Tumor-Associated Antigen Human Papillomavirus-16 E7 (2004)

Previous work in our laboratory has established that the fusion of tumor-associated antigens to a truncated form of the Listeria monocytogenes virulence factor listeriolysin O (LLO) enhances the immunogenicity and antitumor efficacy of the tumor antigen when delivered by Listeria or by vaccinia. LLO contains a PEST sequence at the NH(2) terminus. These sequences, which are found in eukaryotic proteins with a short cellular half-life, target proteins for degradation in the ubiquitin-proteosome pathway. To investigate whether the enhanced immunogenicity conferred by LLO is due to the PEST sequence, we constructed new Listeria recombinants that expressed the HPV-16 E7 antigen fused to LLO, which either contained or had been deleted of this sequence. We then compared the antitumor efficacy of this set of vectors and found that Listeria expressing the fusion protein LLO-E7 or PEST-E7 were effective at regressing established macroscopic HPV-16 immortalized tumors in syngeneic mice. In contrast, Listeria recombinants expressing E7 alone or E7 fused to LLO from which the PEST sequence had been genetically removed could only slow tumor growth. Because CD8(+) T cell epitopes are generated in the ubiquitin-proteosome pathway, we also investigated the ability of the vaccines to induce E7-specific CD8(+) T cells in the spleen and to generate E7-specific tumor-infiltrating lymphocytes. A strong correlation was observed between CD8(+) T-cell induction and tumor homing and the antitumor efficacy of the Listeria-E7 vaccines. These findings suggest a strategy for the augmentation of tumor antigen-based immunotherapeutic strategies that may be broadly applicable.
Patient-Controlled Intranasal Analgesia (1996)

Recently, a new device for patient-controlled intranasal analgesia (PCINA) was described, and a pilot study demonstrated promising results with respect to efficacy and patient satisfaction. The present study compares PCINA with intravenous (IV) patient-controlled analgesia (PCA). Fifty orthopedic patients were prospectively studied over an 8-h period on the first day after surgery. The patients were randomly allocated to PCINA group (n = 25) or to an IV PCA group (n = 25). Pain intensity was evaluated at 30-min intervals using a 101-point numerical rating scale. With respect to initial pain intensity, there was no significant intergroup difference. At the 30- to 480-min measurement points pain intensity in the PCINA group (P < 0.0001) and the IV PCA group (P < 0.0001) was significantly less as compared to the initial value. There was no significant intergroup difference in pain intensity. No patient had problems using the PCINA device. The present study demonstrates, that PCINA provides relief of postoperative pain as effectively as IV PCA. (Anesth Analg 1996;83:548-51)
Nordihydroguaiaretic acid inhibits insulin‐like growth factor signaling, growth, and survival in human neuroblastoma cells (2007)

Neuroblastoma is a common pediatric malignancy that metastasizes to the liver, bone, and other organs. Children with metastatic disease have a less than 50% chance of survival with current treatments. Insulin-like growth factors (IGFs) stimulate neuroblastoma growth, survival, and motility, and are expressed by neuroblastoma cells and the tissues they invade. Thus, therapies that disrupt the effects of IGFs on neuroblastoma tumorigenesis may slow disease progression. We show that NVP-AEW541, a specific inhibitor of the IGF-I receptor (IGF-IR), potently inhibits neuroblastoma growth in vitro. Nordihydroguaiaretic acid (NDGA), a phenolic compound isolated from the creosote bush (Larrea divaricata), has anti-tumor properties against a number of malignancies, has been shown to inhibit the phosphorylation and activation of the IGF-IR in breast cancer cells, and is currently in Phase I trials for prostate cancer. In the present study in neuroblastoma, NDGA inhibits IGF-I-mediated activation of the IGF-IR and disrupts activation of ERK and Akt signaling pathways induced by IGF-I. NDGA inhibits growth of neuroblastoma cells and induces apoptosis at higher doses, causing IGF-I-resistant activation of caspase-3 and a large increase in the fraction of sub-G0 cells. In addition, NDGA inhibits the growth of xenografted human neuroblastoma tumors in nude mice. These results indicate that NDGA may be useful in the treatment of neuroblastoma and may function in part via disruption of IGF-IR signaling.
Endofin, an Endosomal FYVE Domain Protein (2001)

KIAA0305 is an uncharacterized member of the FYVE domain protein family. It is closely related to SARA, with about 50% identity in the carboxyl-terminal 800-amino acid region. Indirect immunofluorescence microscopy using polyclonal antibodies raised against KIAA0305 revealed that it is enriched in early endosomes. The Myc-tagged version is also faithfully targeted to the early endosome. We have tentatively called KIAA0305 endofin (for endosome-associated FYVE-domain protein). The association of endofin with endosomes is mediated by its FYVE domain because deletion mutants lacking the central FYVE finger motif are distributed in the cytoplasm. In addition, a single point mutation in the FYVE finger motif at cysteine residue 753 (C753S) is sufficient to abolish its endosomal association. Its endosomal localization is also sensitive to the phosphatidylinositol 3-kinase inhibitor, wortmannin. Using in vitro liposome binding assays, we demonstrate that Myc-tagged endofin associates preferentially with phosphatidylinositol 3-phosphate, whereas the C753S point mutant was unable to do so. We also show that endofin co-localizes with SARA but that they are not associated in a common complex because they failed to co-immunoprecipitate in co-expressing cells. Endofin also does not associate with Smad2 nor behave like SARA in affecting transforming growth factor-beta signaling. At high levels of expression, both endofin and SARA can cause an endosome aggregation/fusion effect. In COS7 cells, which can support high levels of exogenous protein expression, both proteins can also cause other structural anomalies in the endocytic pathway, as represented by enlarged vesicular structures. These endosomal aggregates/fusions accumulated endocytosed epidermal growth factor. Taken together, this report provides evidence to suggest that endofin and the highly related SARA are endosomal proteins with potential roles in regulating membrane traffic.
Genetically Engineered Antibody Molecules: New Tools for Cancer Therapy (1988)

(1988). Genetically Engineered Antibody Molecules: New Tools for Cancer Therapy. Cancer Investigation: Vol. 6, No. 2, pp. 185-192.