gebhart/patrepeval huggingface dataset:
Trispecific antibodies for CD16A-directed NK cell engagement and dual-targeting of tumor cells (2017)

Bispecific antibodies that redirect the lytic activity of cytotoxic immune effector cells, such as T- and NK cells, onto tumor cells have emerged as a highly attractive and clinically validated treatment modality for hematological malignancies. Advancement of this therapeutic concept into solid tumor indications, however, is hampered by the scarcity of targetable antigens that are surface-expressed on tumor cells but demonstrate only limited expression on healthy tissues. To overcome this limitation, the concept of dual-targeting, i.e. the simultaneous targeting of two tumor-expressed surface antigens with limited co-expression on non-malignant cells, with multispecific antibodies has been proposed to increase tumor selectivity of antibody-induced effector cell cytotoxicity. Here, a novel CD16A (FcγRIIIa)-directed trispecific, tetravalent antibody format, termed aTriFlex, is described, that is capable of redirecting NK cell cytotoxicity to two surface-expressed antigens. Using a BCMA/CD200-based in vitro model system, the potential use of aTriFlex antibodies for dual-targeting and selective induction of NK cell-mediated target cell lysis was investigated. Bivalent bispecific target cell binding was found to result in significant avidity gains and up to 17-fold increased in vitro potency. These data suggest trispecific aTriFlex antibodies may support dual-targeting strategies to redirect NK cell cytotoxicity with increased selectivity to enable targeting of solid tumor antigens.
Oligodendrocyte differentiation and progenitor cell proliferation are independently regulated by cyclic AMP (1993)

Oligodendrocytes, the glial cells specialized to synthesize myelin in the central nervous system, differentiate in primary rat brain cell cultures on a schedule similar to that observed in vivo. The schedule of oligodendrocyte differentiation and the rate of oligodendroglial progenitor cell proliferation in vitro are both modulated by 3',5'-cyclic AMP (cAMP). A 24-hour exposure to 1 mM N6,2'O-dibutyryladenosine 3',5'-cyclic monophosphate (dbcAMP) induced a wave of oligodendrocyte differentiation but inhibited proliferation of oligodendroglial progenitors, and reduced by 30-fold the proliferation of progenitors in response to platelet-derived growth factor (PDGF). When cells were grown in the presence of maximally stimulating concentrations of PDGF, the inhibitory effect of cAMP on progenitor cell proliferation was abolished while the stimulatory effect of cAMP on oligodendrocyte differentiation remained, demonstrating that these two cAMP-regulated events are independent.
Cardiac Angiotensin-(1-7) in Ischemic Cardiomyopathy (2003)

Development of heart failure subsequent to coronary artery ligation leads to increased expression of Ang-(1-7),which was restricted to myocytes.
Expression cloning of a cDNA encoding M1/69-J11d heat-stable antigens. (1990)

The differentiation Ag identified by the mAb M1/69 and J11d (commonly referred to as heat-stable Ag) are found in structurally heterogeneous forms on the surfaces of many types of murine hemopoietic cells. The extinction of expression of these antigens is associated with thymocyte maturation and Ig class switching in B cells, as well as terminal differentiation of macrophages. A cDNA encoding the M1/69-J11d peptide was cloned from a hemopoietic progenitor cell line by immunoselection of COS cells transfected with expression libraries. The cloned cDNA is a copy of a gene that is transcribed in M1/69-J11d+ lymphoid, myeloid, and erythroid cells. This gene could be responsible for the expression of all forms of the M1/69-J11d Ag, although there are homologous genes that may encode some forms of the Ag that are specifically expressed in bone marrow. The cloned cDNA encodes a surprisingly small peptide, predicted to contain only 30 amino acids after removal of a signal sequence and displacement of the C-terminal region by the glycosyl-phosphatidylinositol group that anchors the peptide to the cell surface. Almost all of the mass of the M1/69-J11d Ag accumulates through extensive N- and O-linked glycosylation at multiple sites in the short peptide. These carbohydrates are likely to execute the functions of M1/69-J11d Ag, which could be specialized to each cell type as a consequence of differential glycosylation.
Vascular Endothelial Growth Factor Induces Rapid Phosphorylation of Tight Junction Proteins Occludin and Zonula Occluden 1 (1999)

Vascular endothelial growth factor (VEGF) may have a physiologic role in regulating vessel permeability and contributes to the pathophysiology of diabetic retinopathy as well as tumor development. We set out to ascertain the mechanism by which VEGF regulates paracellular permeability in rats. Intra-ocular injection of VEGF caused a post-translational modification of occludin as determined by a gel shift from 60 to 62 kDa. This event began by 15 min post-injection and was maximal by 45 min. Alkaline phosphatase treatment revealed this modification was caused by a change in occludin phosphorylation. In addition, the quantity of extracted occludin increased 2-fold in the same time frame. The phosphorylation and increased extraction of occludin was recapitulated in retinal endothelial cells in culture after VEGF stimulation. The data presented herein are the first demonstration of a change in the phosphorylation of this transmembrane protein under conditions of increased endothelial permeability. In addition, intra-ocular injection of VEGF also caused tyrosine phosphorylation of ZO-1 as early as 15 min and increased phosphorylation 4-fold after 90 min. In conclusion, VEGF rapidly increases occludin phosphorylation as well as the tyrosine phosphorylation of ZO-1. Phosphorylation of occludin and ZO-1 likely contribute to regulated endothelial paracellular permeability.
Prognostic Values of microRNAs in Colorectal Cancer (2006)

The functions of non-coding microRNAs (miRNAs) in tumorigenesis are just beginning to emerge. Previous studies from our laboratory have identified a number of miRNAs that were deregulated in colon cancer cell lines due to the deletion of the p53 tumor suppressor gene. In this study, the in vivo significance of some of these miRNAs was further evaluated using colorectal clinical samples. Ten miRNAs ( hsa-let-7b, hsa-let-7g, hsa-miR-15b, hsa-miR-181b, hsa-miR-191, hsa-miR-200c, hsa-miR-26a, hsa-miR-27a, hsa-miR-30a-5p and hsa-miR-30c) were evaluated for their potential prognostic value in colorectal cancer patients. Forty eight snap frozen clinical colorectal samples (24 colorectal cancer and 24 paired normal patient samples) with detailed clinical follow-up information were selected. The expression levels of 10 miRNAs were quantified via qRT-PCR analysis. The statistical significance of these markers for disease prognosis was evaluated using a two tailed paired Wilcoxon test. A Kaplan-Meier survival curve was generated followed by performing a Logrank test. Among the ten miRNAs, hsa-miR-15b (p = 0.0278), hsa-miR-181b (p = 0.0002), hsa-miR-191 (p = 0.0264) and hsa-miR-200c (p = 0.0017) were significantly over-expressed in tumors compared to normal colorectal samples. Kaplan-Meier survival analysis indicated that hsa-miR-200c was significantly associated with patient survival (p = 0.0122). The patients (n = 15) with higher hsa-miR-200c expression had a shorter survival time (median survival = 26 months) compared to patients (n = 9) with lower expression (median survival = 38 months). Sequencing analysis revealed that hsa-miR-181b (p = 0.0098) and hsa-miR-200c (p = 0.0322) expression were strongly associated with the mutation status of the p53 tumor suppressor gene. Some of these miRNAs may function as oncogenes due to their over-expression in tumors. hsa-miR-200c may be a potential novel prognostic factor in colorectal cancer.
The Weal and Woe of Costimulation in the Adoptive Therapy of Cancer with Chimeric Antigen Receptor (CAR)-Redirected T Cells (2013)

Adoptive cell therapy has shown impressive efficacy to combat cancer in early phase clinical trials, in particular when T cells engineered to specifically target tumor cells were applied. The patient's T cells are genetically equipped with a chimeric antigen receptor (CAR) which allows them to be redirected in a predefined manner towards virtually any target; by using an antibody-derived domain for binding, CAR T cells can be redirected in a major histocompatibility complex (MHC) dependent and independent fashion. The CAR also provides the stimuli required to induce and maintain T cell activation. Recent clinical data sustain the notion that strong costimulation in conjunction with the primary activation signal is crucial for lasting therapeutic efficacy of CAR T cells. However, costimulation is a double-edged sword and the impact of the individual costimuli to optimize T cell activation is still under debate; some general rules are emerging. The review summarizes how costimulation modulates, improves and prolongs the redirected anti-tumor T cell response and how the same costimulatory signals may contribute to unintended side effects including "cytokine storm" and T cell repression. Upcoming strategies to break the activation/repression circle by using CAR's with modified costimulatory signals are also discussed.
A critical evaluation of mass isotopomer distribution analysis of gluconeogenesis in vivo (1999)

There are conflicting reports concerning the reliability of mass isotopomer distribution analysis (MIDA) for estimating the contribution of gluconeogenesis to total glucose production (f) during [(13)C]glycerol infusion. We have evaluated substrate-induced effects on rate of appearance (R(a)) of glycerol and glucose and f during [2-(13)C]glycerol infusion in vivo. Five groups of mice were fasted for 30 h and then infused with [2-(13)C]glycerol at variable rates and variable (13)C enrichments (group I: 20 micromol. kg(-1). min(-1), 99% (13)C; group II: 60 micromol. kg(-1). min(-1), 60% (13)C; group III: 60 micromol. kg(-1). min(-1), 99% (13)C; group IV: 120 micromol. kg(-1). min(-1), 40% (13)C; or group V: 120 micromol. kg(-1). min(-1), 99% (13)C). The total glycerol R(a) increased from approximately 104 to approximately 157 and to approximately 210 micromol. kg(-1). min(-1) as the infusion of [2-(13)C]glycerol increased from 20 to 60 and to 120 micromol. kg(- 1). min(-1), respectively. As the amount of 99% enriched [2-(13)C]glycerol increased from 20 to 60 and to 120 micromol. kg(-1). min(-1) (groups I, III, and V, respectively), plasma glycerol enrichment increased from approximately 21 to approximately 42 and to approximately 57% and the calculated f increased from approximately 27 to approximately 56 and to approximately 87%, respectively. Similar plasma glycerol enrichments were observed in groups I, II, and IV (i. e., approximately 21-24%), yet f increased from approximately 27 to approximately 57 and to approximately 86% in groups II and IV, respectively. Estimates of absolute gluconeogenesis increased from approximately 14 to approximately 33 and approximately 86 micromol. kg(-1). min(-1) as the infusion of [2-(13)C]glycerol increased from 20 to 60 and 120 micromol. kg(-1). min(-1). Plausible estimates of f were obtained only under conditions that increased total glycerol R(a) approximately 2-fold (P < 0.001) and increased glucose R(a) approximately 1.5-fold (P < 0.01) above basal. We conclude that in 30-h fasted mice, 1) estimates of f by MIDA with low infusion rates of [2-(13)C]glycerol yield erroneous results and 2) reasonable estimates of f are obtained at glycerol infusion rates that perturb glycerol and glucose metabolism.
800 MHz High Power Bandpass Filter using TM Dual Mode Dielectric Resonators (1991)

A novel high power bandpass filter using TM110 dual mode dielectric resonators was developed. TM110 dual mode is achieved with dielectric resonators physically coupled in an asymmetrically orthogonal manner and these arrayed resonators are constructed in monoblock and have high unloaded Q. By assembling these resonators, an 800 MHz high power bandpass filter was realized. Specific features achieved with this new filter are, center frequency of 840 MHz, band width of 40 MHz, and insertion loss of 0.4 dB. Physical size is 80×90×180 mm. Volume is less than 30% of conventional type high power bandpass filter using cavity resonators. This filter is useful as an antenna filter for cellular base stations.
Specific RNA Self-Assembly with Minimal Paranemic Motifs (2007)

The paranemic crossover (PX) is a motif for assembling two nucleic acid molecules using Watson-Crick (WC) basepairing without unfolding preformed secondary structure in the individual molecules. Once formed, the paranemic assembly motif comprises adjacent parallel double helices that crossover at every possible point over the length of the motif. The interaction is reversible as it does not require denaturation of basepairs internal to each interacting molecular unit. Paranemic assembly has been demonstrated for DNA but not for RNA and only for motifs with four or more crossover points and lengths of five or more helical half-turns. Here we report the design of RNA molecules that paranemically assemble with the minimum number of two crossovers spanning the major groove to form paranemic motifs with a length of three half turns (3HT). Dissociation constants (Kd's) were measured for a series of molecules in which the number of basepairs between the crossover points was varied from five to eight basepairs. The paranemic 3HT complex with six basepairs (3HT_6M) was found to be the most stable with Kd = 1 x 10-8 M. The half-time for kinetic exchange of the 3HT_6M complex was determined to be approximately 100 min, from which we calculated association and dissociation rate constants ka = 5.11 x 103 M-1s-1 and kd = 5.11 x 10-5 s-1. RNA paranemic assembly of 3HT and 5HT complexes is blocked by single-base substitutions that disrupt individual intermolecular Watson-Crick basepairs and is restored by compensatory substitutions that restore those basepairs. The 3HT motif appears suitable for specific, programmable, and reversible tecto-RNA self-assembly for constructing artificial RNA molecular machines.
Vocal tract length normalisation approaches to DNN-based children's and adults' speech recognition (2014)

This paper introduces approaches based on vocal tract length normalisation (VTLN) techniques for hybrid deep neural network (DNN) - hidden Markov model (HMM) automatic speech recognition when targeting children's and adults' speech. VTLN is investigated by training a DNN-HMM system by using first mel frequency cepstral coefficients (MFCCs) normalised with standard VTLN. Then, MFCCs derived acoustic features are combined with the VTLN warping factors to obtain an augmented set of features as input to a DNN. In this later, novel, approach the warping factors are obtained with a separate DNN and the decoding can be operated in a single pass when standard VTLN approach requires two decoding passes. Both VTLN-based approaches are shown to improve phone error rate performance, up to 20% relative improvement, compared to a baseline trained on a mixture of children's and adults' speech.
Effects of Nitric Oxide on Slow Waves and Spontaneous Contraction of Guinea Pig Gastric Antral Circular Muscle (2003)

We examined the effects of nitric oxide (NO) donors, S-nitroso-L-cysteine (Cys-NO) and 3-morpholinosydnonimine hydrochloride (SIN-1), on slow waves and contractile activity in the circular muscle of guinea pig gastric antrum. In the presence of atropine and guanethidine, electrical field stimulation (EFS) reduced the amplitude of phasic contraction. The effect of EFS was significantly inhibited by both the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester and a soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Cys-NO and SIN-1 mimicked the effect of EFS on phasic contraction and reduced the amplitude of slow waves in a concentration-dependent manner, with no effect on frequency and resting membrane potential. Phasic contraction was more sensitive to NO donors than slow waves. The inhibitory effects of NO donors were antagonized by ODQ and mimicked by a membrane permeable cGMP analogue 8-bromo-cGMP. Several K(+) channel blockers such as apamin, iberiotoxin, and glibenclamide had no effect on the inhibitory action of SIN-1. These results suggest that NO inhibits the phasic contraction and slow waves through cGMP-dependent mechanisms in guinea pig gastric antrum. The effect of NO is unlikely to be mediated by the activation of Ca(2+)-activated or ATP-sensitive K(+) channels.
Vaccine assembly from surface proteins of Staphylococcus aureus (2006)

Staphylococcus aureus is the most common cause of hospital-acquired infection. Because of the emergence of antibiotic-resistant strains, these infections represent a serious public health threat. To develop a broadly protective vaccine, we tested cell wall-anchored surface proteins of S. aureus as antigens in a murine model of abscess formation. Immunization with four antigens (IsdA, IsdB, SdrD, and SdrE) generated significant protective immunity that correlated with the induction of opsonophagocytic antibodies. When assembled into a combined vaccine, the four surface proteins afforded high levels of protection against invasive disease or lethal challenge with human clinical S. aureus isolates.
Androgen antagonist activity by the antioxidant moiety of vitamin E, 2,2,5,7,8-pentamethyl-6-chromanol in human prostate carcinoma cells. (2003)

Antioxidants, such as vitamin E, are being investigated for efficacy in prostate cancer prevention. In this study, we show that the antioxidant moiety of vitamin E, 2,2,5,7,8-pentamethyl-6-chromanol (PMCol), has antiandrogen activity in prostate carcinoma cells. In the presence of PMCol, the androgen-stimulated biphasic growth curve of LNCaP human prostate carcinoma cells was shifted to the right. The PMCol-induced growth shift was similar to that produced by treatment with the pure antiandrogen bicalutamide (i.e., Casodex), indicative of androgen receptor (AR) antagonist activity. The concentration of PMCol used was below the concentration required to affect cell growth or viability in the absence of androgen. Using an AR binding competition assay, PMCol was found to be a potent antiandrogen in both LNCaP and LAPC4 cells, with an IC(50) of approximately 10 micro M against 1 nM R1881 (methyltrienolone; a stable, synthetic androgen). Prostate-specific antigen release from LNCaP cells produced by androgen exposure with either 0.05 or 1.0 nM R1881 was inhibited 100% and 80%, respectively, by 30 micro M PMCol. Also, PMCol inhibited androgen-induced promoter activation in both LNCaP and LAPC4 cells. However, PMCol did not affect AR protein levels, suggesting that the inhibitory effects of PMCol on androgenic pathways were not due to decreased expression of the AR. Therefore, growth modulation by the antioxidant moiety of vitamin E in androgen-sensitive prostate carcinoma cells is due, at least in part, to its potent antiandrogenic activity.
Generalized privacy amplification (1995)

This paper, provides a general treatment of privacy amplification by public discussion, a concept introduced by Bennett, Brassard, and Robert for a special scenario. Privacy amplification is a process that allows two parties to distil a secret key from a common random variable about which an eavesdropper has partial information. The two parties generally know nothing about the eavesdropper's information except that it satisfies a certain constraint. The results have applications to unconditionally secure secret-key agreement protocols and quantum cryptography, and they yield results on wiretap and broadcast channels for a considerably strengthened definition of secrecy capacity.
CD4 and p56lck can stably associate when co-expressed in NIH3T3 cells. (1989)

The CD4 T-cell surface antigen and the lymphocyte-specific tyrosine-protein kinase p56lck form a stable noncovalent complex in CD4+ T-lymphocytes. In this report, we demonstrate that these two gene products can also associate when co-expressed in NIH3T3 fibroblasts, therefore implying that other lymphoid specific components are not required for the CD4-lck interaction. These results also suggest that co-expression of CD4 and p56lck in non-lymphoid cells may prove to be a useful model system for the analysis of structural and possibly functional CD4-lck interactions.
Synthesis, characterization, and enzymatic degradation of network aliphatic copolyesters (1999)

Network copolyesters were prepared from glycerol (Yg) and sebacic acid (10) with 10–90 mol % of either succinic acid (4), 1,12-dodecanedicarboxylic acid (14), 1,18-octadecanedicarboxylic acid (20), or terephthalic acid (T). Prepolymers prepared by melt-polycondensation were cast from dimethylformamide solution and postpolymerized at 230–250°C for various periods of time to form a network. The resultant films were transparent, flexible, and insoluble in organic solvents. The network copolyesters obtained were characterized by infrared absorption spectra, wide angle X-ray diffraction analysis, density measurement, thermomechanical analysis, differential scanning calorimetry, and tensile test. The enzymatic degradation was estimated by weight loss of the network copolyester films in a buffer solution with Rhizopus delemar lipase at 37°C. The weight loss due to the enzymatic degradation was decreased with increasing comonomer content, and the copolyesters with Yg4, Yg20 and YgT more than 50 mol % were not degraded by lipase enzyme at all. On the contrary, Yg-10/14 films were degraded appreciably over whole range of comonomer composition. With increasing comonomer content, the heat distortion temperature increased gradually, while the tensile strength and Young's modulus were not changed much. © 1999 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 37: 2005–2011, 1999
Assessment and Optimization of chemical and physicochemical Softening Processes (2002)

Hardness removal processes are very pH‐dependent, especially for removal of magnesium (Mg) and silica (Si). Bench‐scale tests were conducted with a groundwater that was supersaturated with carbon dioxide and contained calcium (Ca), Mg, and Si. The purpose of this work was to assess and optimize several softening processes to reduce chemical use (i.e., sludge production) and improve turbidity removal. Optimal dosing of lime and soda ash (OLSA) removed 79% of Ca and Mg hardness and 23% of Si hardness. Iron salt addition during OLSA improved the rate of turbidity removal, had minimal effect on Ca or Si removal, but decreased Mg removal unless the pH was readjusted to offset the pH decline that resulted from iron hydroxide formation. Sodium aluminate addition during OLSA improved the rate of turbidity removal and increased settled sludge viscosity, but did not affect Ca, Mg, or Si removal. In separate semibatch aeration softening tests (without lime or soda ash addition), Ca removal increased as a function of aeration rates; Mg and Si were not removed. The addition of a nuclei seed increased dissolved Ca removal from 60% without the nuclei seed to &gt; 80% in the presence of 3 g/L of nuclei seed. Results indicate that the aeration softening process would remove hardness, decrease chemical consumption, and reduce sludge production.